Docking Research Papers - Academia.edu (original) (raw)

A new series of sulfonamide derivatives of pyrazolo[4,3-e][1,2,4]triazine has been synthesized and characterized. Their anticancer activity was tested in vitro against multiple human cancer cell lines and were found to have dose-dependent antiproliferative effects. Furthermore, some of the new compounds inhibited the Abl protein kinase with low micromolar IC 50 values and exhibited selective activity against the Bcr-Abl positive K562 and BV173 cell lines, providing starting points for the further development of this new kinase inhibitor scaffold.

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- Organic Chemistry, Cancer, Molecular docking, Docking
- by Nidhi Arora
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- Thermodynamics, Chemistry, Electrostatics, Medicine

Two-component systems (TCSs) are the major signalling pathway in bacteria and represent potential drug targets. Among the 11 paired TCS proteins present in Mycobacterium tuberculosis H37Rv, the histidine kinases (HKs) Rv0600c (HK1) and Rv0601c (HK2) are annotated to phosphorylate one response regulator (RR) Rv0602c (TcrA). We wanted to establish the sequence-structure-function relationship to elucidate the mechanism of phosphotransfer using in silico methods. Sequence alignments and codon usage analysis showed that the two domains encoded by a single gene in homologous HKs have been separated into individual open-reading frames in M. tuberculosis. This is the first example where two incomplete HKs are involved in phosphorylating a single RR. The model shows that HK2 is a unique histidine phosphotransfer (HPt)-mono-domain protein, not found as lone protein in other bacteria. The secondary structure of HKs was confirmed using ''far-UV'' circular dichroism study of purified proteins. We propose that HK1 phosphorylates HK2 at the conserved H 131 and the phosphoryl group is then transferred to D 73 of TcrA.

Selecting near-native conformations from the immense number of conformations generated by docking programs remains a major challenge in molecular docking. We introduce DockRank, a novel approach to scoring docked conformations based on the degree to which the interface residues of the docked conformation match a set of predicted interface residues. DockRank uses interface residues predicted by partner-specific sequence homology-based protein–protein interface predictor (PS-HomPPI), which predicts the interface residues of a query protein with a specific interaction partner. We compared the performance of DockRank with several state-of-the-art docking scoring functions using Success Rate (the percentage of cases that have at least one near-native conformation among the top m conformations) and Hit Rate (the percentage of near-native conformations that are included among the top m conformations). In cases where it is possible to obtain partner-specific (PS) interface predictions from PS-HomPPI, DockRank consistently outperforms both (i) ZRank and IRAD, two state-of-the-art energy-based scoring functions (improving Success Rate by up to 4-fold); and (ii) Variants of DockRank that use predicted interface residues obtained from several protein interface predictors that do not take into account the binding partner in making interface predictions (improving success rate by up to 39-fold). The latter result underscores the importance of using partner-specific interface residues in scoring docked conformations. We show that DockRank, when used to re-rank the conformations returned by ClusPro, improves upon the original ClusPro rankings in terms of both Success Rate and Hit Rate. DockRank is available as a server at http://einstein.cs.iastate.edu/DockRank/.

Aim: Cancer is a serious disease that not fully defined now-a-days. The problem of cancer is the metastatis, and the unnatural proliferation of the cell. Many chemotherapeutic agents are used to treat cancer, but they failed to cure the cancer patient. They may prevent some of the portion but not totally defend against cancer. So our work devoted to design a novel chemotherapeutic agent with minimal sideeffects against prostate cancer.

- by Vijey Aanandhi M
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- Prostate Cancer, Docking, Mannich base

Ligands that activate the serotonin 5-HT 2C G protein-coupled receptor (GPCR) may be therapeutic for psychoses, addiction, and other neuropsychiatric disorders. Ligands that are antagonists at the closely related 5-HT 2A GPCR also may treat neuropsychiatric disorders; in contrast, 5-HT 2A activation may cause hallucinations. 5-HT 2C-specific agonist drug design is challenging because 5-HT 2 GPCRs share 80% transmembrane (TM) homology, same second messenger signaling, and no crystal structures are reported. To help delineate molecular determinants underlying differential binding and activation of 5-HT 2 GPCRs, 5-HT 2A , and 5-HT 2C homology models were built from the β 2-adrenergic GPCR crystal structure and equilibrated in a lipid phosphatidyl choline bilayer performing molecular dynamics simulations. Ligand docking studies at the 5-HT 2 receptor models were conducted with the (2R, 4S)-and (2S, 4R)-enantiomers of the novel 5-HT 2C agonist/5-HT 2A/2B antagonist trans-4-phenyl-N,N-dimethyl-2-aminotetralin (PAT) and its 4′-chlorophenyl congners. Results indicate PAT-5-HT 2 molecular interactions especially in TM domain V are important for the (2R, 4S) enantiomer, whereas, TM domain VI and VII interactions are more important for the (2S, 4R) enantiomer.

- by Tania C Cordova-Sintjago
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- Quantum Chemistry, Molecular Dynamics, Drug Design, GPCR

Conception d'un logiciel de docking et applications dans la recherche de nouvelles molécules actives. 8/90 dans l'espoir de soulager voire guérir ceux qui souffrent et, pourquoi pas, de prolonger encore un peu nos vies. Conception d'un logiciel de docking et applications dans la recherche de nouvelles molécules actives. 12/90 Conception d'un logiciel de docking et applications dans la recherche de nouvelles molécules actives. 74/90 Conception d'un logiciel de docking et applications dans la recherche de nouvelles molécules actives. 75/90

- by Aurélien Grosdidier
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- Docking, Ligand

Depression associated with poor general medical condition, such as post-stroke (PSD) or post-myocardial infarction (PMID) depression, is characterized by resistance to classical antidepressants. Special treatment strategies should thus be developed for these conditions. Our study aims to investigate the mechanism of action of 2-morpholino-5-phenyl-6H-1,3,4-thiadiazine, hydrobromide (L-17), a recently designed thiadiazine derivative with putative neuro- and cardioprotective and antidepressant-like effects, using combined in silico (for prediction of the molecular binding mechanisms), ex vivo (for assessment of the neural excitability using c-Fos immunocytochemistry), and in vivo (for direct examination of the neuronal excitability) methodological approaches. We found that the predicted binding affinities of L-17 to serotonin (5-HT) transporter (SERT) and 5-HT3 and 5-HT1A receptors are compatible with selective 5-HT serotonin reuptake inhibitors (SSRIs) and antagonists of 5-HT3 and 5-HT1A receptors, respectively. L-17 robustly increased c-Fos immunoreactivity in the amygdala and decreased it in the hippocampus. L-17 dose-dependently inhibited 5-HT neurons of the dorsal raphe nucleus; this inhibition was partially reversed by the 5-HT1A antagonist WAY100135. We suggest that L-17 is a potent 5-HT reuptake inhibitor and partial antagonist of 5-HT3 and 5-HT1A receptors; the effects of L-17 on amygdaloid and hippocampal excitability might be mediated via 5-HT, and putatively mediate the antidepressant-like effects of this drug. Since L-17 also possesses neuro- and cardioprotective properties, it can be beneficial in PSD and PMID. Combined in silico predictions with ex vivo neurochemical and in vivo electrophysiological assessments might be a useful strategy for early assessment of the efficacy and neural mechanism of action of novel CNS drugs.

Total USD = USD 37, 753-Price difference if permanent repair carried out = USD45,800-37,753 = about USD8000.00 Soft patched 370mm L = 3390mm OD = 414mm Judgment: We anticipated that, during the last repair, machining down of sleeve up to its permissible tolerance (6mm) was not achievevable. It meant that, it was expected that though the sleeve is machined down up to the max permissible, the porosities (due to corrosion) still can't be removed. Thus, the sleeve was slightly machined down and its surfaces were smoothened by Belzona. 31/08/2014-afloat repair at accessible area only with DEVCON – minor patch-up-used spare seal-Belzona coating was in bad condition + broken – (detached)

- by WB Jones
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- History, Maritime History, Local History, Labour history

Mutu Dewasa ini sistem yang terdapat di dalam organisasi dapat mempengaruhi pelanggan untuk mencoba produk baru yang ditawarkan organisasi, dan kemudian tetap setia untuk terus memakai produk yang ditawarkan organisasi terebut. Semakin mudah pelanggan untuk mendapatkan produk yang ditawarkan organisasi melalui kemudahan sistem yang ada, semakin setia pula pelanggan memakai produk yang ditawarkan organisasi tersebut. Oleh karena itu, terdapat suatu standar untuk sistem yang diterapkan oleh manajemen, semakin baik sistem yang diterapkam manajemen dalam organisasi, maka semakin mudah bagi organisasi untuk mendapatkan standar Internasional bagi penerapan sistem manajemen di dalam organisasinya. ISO 9001:2000 adalah suatu standar internasional untuk sistem manajemen mutu. ISO 9001:2000 menetapkan persyaratan-persyaratan dan rekomendasi untuk desain dan penilaian dari sistem manajemen mutu. Manajemen mutu dapat dianggap memiliki tiga komponen utama: pengendalian mutu, jaminan mutu dan perbaikan mutu. Manajemen mutu berfokus tidak hanya pada mutu produk, namun juga cara untuk mencapainya. Manajemen mutu menggunakan jaminan mutu dan pengendalian terhadap proses dan produk untuk mencapai mutu secara lebih konsisten. b. Pengendalian Mutu dalam Proses Pengedokan Kapal Docking Kapal adalah suatu peristiwa pemindahan kapal dari air/laut ke atas dock dengan bantuan fasilitas docking/pengedockan. Untuk melakukan pengedokan kapal ini, harus dilakukan persiapan yang matang dan berhati-hati mengingat spesifikasi kapal yang berbeda-beda. Mengingat besarnya biaya yang dikeluarkan pihak owner dalam melakukan proses repair/perbaikan kapal. Maka diperlukan perhatian serius dalam proses memasukkan kapal naik ke dry dock. Hal ini dikarenakan saat-saat kapal yang paling ekstrem adalah pada saat setengah badan kapal kering dan setengah basah. Kehati-hatian dengan tetap mempertahankan kualitas mutu merupakan kunci dari proses pengedokan yang sukses. Standar mutu yang baik perlu disiapkan oleh pihak galangan dan owner demi kelancaran proses dari awal kapal datang ke galangan sampai naik 100 persen ke atas dok. Grafik flowchart proses administrasi dan doking repair kapal di galangan

- by Arnan Abdurrofi
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- Engineering, Naval Architecture, University, Docking

One of the fundamental challenges in designing drug molecule against a disease target or protein is to predict binding affinity between target and drug or small molecule. In this review, our focus will be on advancement in the field of protein-small molecule interaction. This review has been divided into four major sections. In the first section, we will cover software developed for protein structure prediction. This will include prediction of binding pockets and post-translation modifications in proteins. In the second section, we will discuss software packages developed for predicting small-molecule interacting residues in a protein. Advances in the field of docking particularly advancement in the knowledge-based force fields will be discussed in the third part of the review. This section will also cover the method developed for predicting affinity between protein and drug molecules. The fourth section of the review will describe miscellaneous techniques used for designing drug molecules, like pharmacophore modelling. Our major emphasis in this review will be on computational tools that are available free for academic use.

Virtual screening (VS) is a powerful technique for identifying hit molecules as starting points for medicinal chemistry. The number of methods and softwares which use the ligand and target-based VS approaches is increasing at a rapid pace. What, however, are the real advantages and disadvantages of the VS technology and how applicable is it to drug discovery projects? This review provides a comprehensive appraisal of several VS approaches currently available. In the first part of this work, an overview of the recent progress and advances in both ligand-based VS (LBVS) and structurebased VS (SBVS) strategies highlighting current problems and limitations will be provided. Special emphasis will be given to in silico chemogenomics approaches which utilize annotated ligand-target as well as protein-ligand interaction databases and which could predict or reveal promiscuous binding and polypharmacology, the knowledge of which would help medicinal chemists to design more potent clinical candidates with fewer side effects. In the second part, recent case studies (all published in the last two years) will be discussed where the VS technology has been applied successfully. A critical analysis of these case studies provides a good platform in order to estimate the applicability of various VS strategies in the new lead identification and optimization.

Computational methods play a central role in modern drug discovery process. It includes the design and management of small molecule libraries, initial hit identification through virtual screening, optimization of the affinity as well as selectivity of hits and improving the physicochemical properties of the lead compounds. In this review article, computational drug designing approaches have been elucidated and discussed. The key considerations and guidelines for virtual chemical library design and whole drug discovery process. Traditional approach for discovery of a new drug is a costly and time consuming affair besides not being so productive. A number of potential reasons witness choosing the In-silico method of drug design to be a more wise and productive approach. There is a general perception that applied science has not kept pace with the advances of basic science. Therefore, there is a need for the use of alternative tools to get answers on efficacy and safety faster, with more certainty and at lower cost. In-silico drug design can play a significant role in all stages of drug development from the initial lead designing to final stage clinical development.

- by IJPBR Journal
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- Bioinformatics, Computational Biology, Virtual screening, Docking

Background: Protein-based pharmacophore models are enriched with the information of potential interactions between ligands and the protein target. We have shown in a previous study that protein-based pharmacophore models can be applied for ligand pose prediction and pose ranking. In this publication, we present a new pharmacophore-based docking program PharmDock that combines pose sampling and ranking based on optimized protein-based pharmacophore models with local optimization using an empirical scoring function.

- by Markus Lill
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- Cheminformatics, GUI, Docking

The understanding and optimization of proteinligand interactions are instrumental to medicinal chemists investigating potential drug candidates. Over the past couple of decades, many powerful standalone tools for computer-aided drug discovery have been developed in academia providing insight into protein-ligand interactions. As programs are developed by various research groups, a consistent user-friendly graphical working environment combining computational techniques such as docking, scoring, molecular dynamics simulations, and free energy calculations is needed. Utilizing PyMOL we have developed such a graphical user interface incorporating individual academic packages designed for protein preparation (AMBER package and Reduce), molecular mechanics applications (AMBER package), and docking and scoring (AutoDock Vina and SLIDE). In addition to amassing several computational tools under one interface, the computational platform also provides a user-friendly combination of different programs. For example, utilizing a molecular dynamics (MD) simulation performed with AMBER as input for ensemble docking with AutoDock Vina. The overarching goal of this work was to provide a computational platform that facilitates medicinal chemists, many who are not experts in computational methodologies, to utilize several common computational techniques germane to drug discovery. Furthermore, our software is open source and is aimed to initiate collaborative efforts among computational researchers to combine other open source computational methods under a single, easily understandable graphical user interface.

- by Markus Lill
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- Computer Aided Design, Drug Discovery, Molecular modeling, Work Environment

In the present investigation, a series of 12 Mannich bases (QP1-12) and 5 Schiff bases (QSP1-5) of pyrazol-5(4H)one moiety containing 3-(hydrazinyl)-2-phenylquinazolin-4(3H)-one has been synthesized and characterized by physicochemical as well as spectral means. The synthesized Mannich and Schiff bases were screened for their preliminary antimicrobial activity against Gram-positive and Gram-negative bacterial as well as fungal strains by the determination of zone of inhibition. Mannich bases (QP1-12) were found to be more potent antibacterial agents against Gram-positive bacteria, whereas Schiff bases (QSP1-5) were more potent against Gram-negative bacteria and fungi. Minimum inhibitory concentration result demonstrated that Mannich base compound (QP7) having ortho -OH and para -COOH group showed some improvement in antibacterial activity (minimum inhibitory concentration of 48.88×10 −3 μM/ml) among the tested Gram-positive organisms and it also exhibit minimum inhibitory concentration of value of 12.22×10 −3 μM/ml for Klebsiella pneumoniae. The antitubercular activity of synthesized compounds against Mycobacterium tuberculosis (H 37 Rv) was determined using microplate alamar blue assay. Compound QP11 showed appreciable antitubercular activity (minimum inhibitory concentration of 6.49×10 −3 μM/ml) which was more active than the standard drugs, ethambutol (minimum inhibitory concentration of 7.60×10 −3 μM/ml) and ciprofloxacin (9.4×10 −3 μM/ml). Compounds QP11, QP9, QSP1, QSP2, and QSP5 have good selective index and may be selected as a lead compound for the development of novel antitubercular agents.

- by siva kumar
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- Medicinal Chemistry, Docking

Pattern recognition, machine learning and artificial intelligence approaches play an increasingly important role in rational drug design, screening and identification of candidate molecules and studies on quantitative structure-activity relationships (QSAR). In this review, we present an overview of basic concepts and methodology in the fields of machine learning and artificial intelligence (AI). An emphasis is put on methods that enable an intuitive interpretation of the results and facilitate gaining an insight into the structure of the problem at hand. We also discuss representative applications of AI methods to docking, screening and QSAR studies. The growing trend to integrate computational and experimental efforts in that regard and some future developments are discussed. In addition, we comment on a broader role of machine learning and artificial intelligence approaches in biomedical research.

- by Jarek Meller and +1
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- Artificial Intelligence, Design, Machine Learning, Computational Biology

An In silico study was carried out on a series of novel quinoline based inhibitors which were designed, synthesized and assessed for their in vitro activity versus the human colon cancer cell line HT29 and the human breast cancer cell line MDA-MB231 by Arafa RK et. al. We have designed these 22 inhibitors in ChemBioOffice 2010 and minimized using the LigPrep tool of Schrödinger 2011. Docking study of these inhibitors was performed on different cancer proteins in order to give a suggestion to the proposed in vitro mechanism of action. Some prominent cancer proteins specifically causing breast and colon cancers are used as targets in this computational study to predict the most active quinoline based derivative. The proteins are minimized using the protein preparation wizard and Grid is generated by specifying the active site amino acids. The binding model of best scoring inhibitor with each protein was assessed from their G-scores and disclosed by docking analysis using the XP visualizer tool. Interestingly the result of docking was found to match with the previous invitro study where the most active derivative against both tested cell lines was the Schiff's base 4e. The pharmacokinetic parameters study was done using the QikProp 3.4 tool to display ADME and toxicity properties of these inhibitors.

- by Manoj Kumar
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- Cancer, Docking, Quinoline, ADME

The present study details about the molecular docking of a series of novel Azetidinone derivatives in to the binding site of COX-2. These Azetidinone derived from condensation different substituted. Thiophene Schiff bases with chloro acetyl chloride. 1CX2 in which COX-2 co-crystallized with potent selective inhibitors SC558 has been chosen as target protein molecule for the present investigation. Autodock 4.2.1 was used to perform the molecular docking studies. Initially docking methodology has been validated by using potent inhibitor SC558, later all selected ligands were docked in to the same binding site of COX-2. From the results of docking studies binding energies and binding poses of all docked ligands were determined. Finally the binding interactions of best rank conformation of each ligand were analyzed. The binding interactions of ligands were compared with SC558, and found that compounds 3d, 3e, 3f, 3h 4e and 4f were found to show best fit in the binding site of COX-2 under study with least binding energies.

- by Naresh k
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- Biochemistry, Bioinformatics, Medicinal Chemistry, Inflammation

In spatial agent-based models (SABMs) each entity of the system being modeled is uniquely represented as an independent agent. Large scale emergent behavior in SABMs is population sensitive. Thus, the number of agents should reflect the system being modeled, which can be in the order of billions. Models can be decomposed such that each component can be concurrently processed by a different thread. In this thesis, a conceptual model for investigating parallelization strategies for SABMs is presented. The model, PPHPC, captures important characteristics of SABMs. NetLogo, Java and OpenCL (CPU and GPU) implementations are proposed. To confirm that all implementations yield the same behavior, their outputs are compared using two methodologies. The first is based on common model comparison techniques found in literature. The second is a novel approach which uses principal component analysis to convert simulation output into a set of linearly uncorrelated measures which can be analyzed in a model-independent fashion. In both cases, statistical tests are applied to determine if the implementations are properly aligned. Results show that most implementations are statistically equivalent, with lower-level parallel implementations offering substantial speedups. The PPHPC model was shown to be a valid template model for comparing SABM implementations.

This paper proposes a method for the visual-based navigation of a mobile robot in indoor environments, using a single omni-directional (catadioptric) camera. The geometry of the catadioptric sensor and the method used to obtain a bird's eye (orthographic) view of the ground plane are presented. This representation significantly simplifies the solution to navigation problems, by eliminating any perspective effects.

- by Jose Gaspar
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- Mechanical Engineering, Topology, Motion Planning, Path planning

Setiap galangan pasti memiliki keuntungan dan kelemahan yang berbeda-beda. Sama halnya dengan GEMAK Shipyard, galangan ini tentunya mempunyai keuntungan dan kelemahan yang berbeda dengan galangan yang lain. Kelemahan tersebut dapat berupa buruknya material handling, kurangnya jumlah crane, dll. Maka, kami mencoba menjabarkan masing-masing kelebihan dan kelemahan galangan ini dan membuat solusi atas kelemahan-kelemahan yang ada, sehingga nilai ekonomis suatu galangan dapat meningkat seiring meningkatnya produktivitas galangan tersebut.

- by Arnan Abdurrofi
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- Naval Engineering, Naval Architecture, Indonesia, Turkey

Benzimidazole-2-carbamate derivatives (BzCs) are the most commonly used antiparasitic drugs for the treatment of protozoan and helminthic infections. BzCs inhibit the microtubule polymerization mechanism through binding selectively to the ␤-tubulin subunit in which mutations have been identified that lead to drug resistance. Currently, the lack of crystallographic structures of ␤-tubulin in parasites has limited the study of the binding site and the analysis of the resistance to BzCs. Recently, our research group has proposed a model to explain the interaction between the BzCs and a binding site in the ␤tubulin. Herein, we report the homology models of two susceptible (Haemonchus contortus and Giardia intestinalis) parasites and one unsusceptible (Entamoeba histolytica) generated using the structure of the mammal Ovis aries, considered as a low susceptible organism, as a template. Additionally, the mechanism by which the principal single point mutations Phe167Tyr, Glu198Ala and Phe200Tyr could lead to resistance to BzCs is analyzed. Molecular docking and molecular dynamics studies were carried out in order to evaluate the models and the ligand-protein complexes' behaviors. This study represents a first attempt towards understanding, at the molecular level, the structural composition of ␤-tubulin in all organisms, also suggesting possible resistance mechanisms. Furthermore, these results support the importance of benzimidazole derivative optimization in order to design more potent and selective (less toxic) molecules for the treatment of parasitic diseases.

- by Rafael Castillo
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- Molecular Dynamics Simulation, Molecular Dynamics, Homology Modeling, Phylogeny

KD PERANTAU menaiki galangan pada beban keseluruhan melebihi +-300 tan (air dan lumpur) drpd deadweight. Lebihan bebanan ini di buang secara berperingkat dan selesai lebih kurang 3 minggu selepas berada di atas galangan. Soalan saya. Adakah lebihan bebanan ni menjejaskan struktur kapal? Sekiranya ya, apakah cadangan Encik Muzammil utk saya bangkitkan isu ini kpd Boustead? Answers: In principal, vessels are designed to operate at her "max global hull girder bending moment and shear force limits It means that the vessel principle global and local strength shall withstand: Component of Min. Vessel's strength (global+local) = Hull girder bending moment (BM) and shear strength(S) = Static loads + dynamic loads = [(Internal load + external load)] + [(wave+ wind load)] = [(displacement load + static sea pressure)] + [(wave+ wind load)] Where: Vessel displacement load, = max design total weight = max design lightweight (LW) + deadweight (DW)

Among the various parasitic diseases, malaria is the deadliest one. Due to the emergence of high drug resistance to the existing drug candidates there is a global need for development of new drug candidates which will be effective against resistant strains of malaria parasite. In silico molecular modeling approaches have been playing an important role in the discovery of novel lead molecules having antimalarial activity. Present review is an effort to cover all the developments related to the application of computational techniques for the design and discovery of novel antimalarial compounds since the year 2011 onwards.

- by Prashant Murumkar and +1
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- Pharmacology, Biochemistry, Bioinformatics, Chemistry

Novel (thio)phosphoramidate derivatives based on piperidincarboxamide with the general formula of (NH 2 –C(O)–C 5 H 9 N)–P(X = O,S)R 1 R 2 (1–5) and (NH 2 –C(O)–C 5 H 9 N) 2 –P(O)R (6–9) were synthesized and characterized by 31 P, 13 C, 1 H NMR, IR spectroscopy. Furthermore, the crystal structure of compound (NH 2 –C(O)–C 5 H 9 N) 2 –P(O)(OC 6 H 5) (6) was investigated. The activities of derivatives on cholinesterases (ChE) were determined using a modified Ellman's method. Also the mixed-type mechanisms of these compounds were evaluated by Lineweaver–Burk plots. Molecular docking and quantitative structure– activity relationship (QSAR) were used to understand the relationship between molecular structural features and anti-ChE activity, and to predict the binding affinity of phosphoramido-piperidinecarboxamides (PAPCAs) to ChE receptors. From molecular docking analysis, noncovalent interactions especially hydrogen bonding as well as hydrophobic was found between PAPCAs and ChE. Based on the docking results, appropriate molecular structural parameters were adopted to develop a QSAR model. DFT-QSAR models for ChE enzymes demonstrated the importance of electrophilicity parameter in describing the anti-AChE and anti-BChE activities of the synthesized compounds. The correlation matrix of QSAR models and docking analysis confirmed that electrophilicity descriptor can control the influence of the hydrophobic properties of P = (O, S) and C@O functional groups of PAPCA derivatives in the inhibition of human ChE enzymes.

- by Mahyar Bonsaii
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- Inorganic Chemistry, Enzyme Inhibitors, QSAR, Pesticides

Human purine nucleoside phosphorylase (HsPNP) is a target for inhibitor development aiming at T-cell immune response modulation. In this work, we report the development of a new set of empirical scoring functions and its application to evaluate binding affinities and docking results. To test these new functions, we solved the structure of HsPNP and 2-mercapto-4(3H)-quinazolinone (HsPNP:MQU) binary complex at 2.7 Å resolution using synchrotron radiation, and used these functions to predict ligand position obtained in docking simulations. We also employed molecular dynamics simulations to analyze HsPNP in two conditions, as apoenzyme and in the binary complex form, in order to assess the structural features responsible for stability. Analysis of the structural differences between systems provides explanation for inhibitor binding. The use of these scoring functions to evaluate binding affinities and molecular docking results may be used to guide future efforts on virtual screening focused on HsPNP.

- by Rafael Caceres
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- Enzymology, Immune response, Kinetics, Synchrotron Radiation
- by Visvaldas Kairys
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- Computational Biology, Docking, Structural model, Biochemistry and cell biology

Artemether (ARM) is a poorly water soluble and poorly permeable drug effective against acute and severe falciparum malaria, hence there is a strong need to improve its solubility. The objective of the study was to enhance the solubility and dissolution rate of ARM by preparation of solid dispersions using spray-drying technique. Solid dispersions of ARM were prepared with Soluplus, Kollidon VA 64, HPMC and Eudragit EPO at weight ratios of 1:1, 1:2, 1:3 using spray drying technology, and characterized by Fourier transform infrared spectroscopy, differential scanning calorimetry (DSC), and X-ray powder diffraction (XRD) to identify the physicochemical interaction between drug and carrier, as well as effect on dissolution.

- by JAYWANT` Pawar and +2
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- Chemistry, Docking, Solid Dispersion, Spray Drying

- by Carmen Di Giovanni
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- Genomics, Drug Discovery, Drug discovery (Biology), Chemogenomics

The aim of the current study was to investigate the vasorelaxant activity of five structurally-related triterpenic acids namely ursolic (1), moronic (2), morolic (3), betulinic (4) and 3,4-seco-olean-18-ene-3,28-dioic (5) acids. The vasorelaxant effect of compounds 1-5 were determined on endothelium-denuded and endothelium-intact rat aortic rings pre-contracted with noradrenaline (0.1 μM). All compounds showed significant relaxant effect on endothelium-intact vessels in a concentration-dependent manner (pb 0.05). Ursolic, moronic and betulinic acids were the most potent vasorelaxant agents with 11.7, 16.11 and 58.46 μM, respectively. Since vasorelaxation was blocked by L-NAME, while indomethacin did not inhibit the effect, endothelium-derived nitric oxide seems to be involved in triterpenic 2 and 3 mode of action. Compounds 1-5 were docked with a crystal structure of eNOS. Triterpenes 1-5 showed calculated affinity with eNOS in the C1 and C2 binding pockets, near the catalytic site; Ser248 and Asp480 are the residues that make hydrogen bonds with the triterpene compounds.

- by habby zikril hakim
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- Docking

Snake envenomation is a serious health issue in all over the world. In India Naja naja (Indian Cobra) is one among the four common venomous snakes which cause high rate of mortality and morbidity. Antivenom therapy is the only treatment in modern medicine but it has several limitations including serious side effects to the patients. Most of the snake bite victims still relay on herbal medicine which cause less side effects than the immunotherapy. But its efficacy and mode of drug activities are seldom investigated. In silico screening is best option to identify the lead compounds and demonstrate the drug activity.

- by Krishnan Peringattulli
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- Pharmacology, Biochemistry, Bioinformatics, Pharmacy

Human Immunodeficiency virus is an existing pathogen for which the development of drugs, vaccines, anti viral therapy has seen little success. The HIV-1 Integrase(HIV-1 IN) is a potential target for antiviral drugs since it plays a vital role in facilitating the integration of viral DNA into the host cell genome. Our present quest concentrates on discovering anti HIV compounds that are present in the ethanolic extract of Nilavembu (Andrographis panniculata Nees). It is an important medicinal herb belonging to the family Acanthaceae. The phytochemicals extracted from Andrographis panniculata were docked against the enzyme HIV-1 integrase. The results reveal that those compounds are active against HIV-1 integrase and will be effective for doing further research on plant Andrographis panniculata in drug designing against HIV.

- by Ramanan Subramanian
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- Biochemistry, Bioinformatics, Chemistry, Immunology

A series of novel purine and pyrimidine derivatives were prepared and biologically evaluated for their in vitro anti-CDK2/cyclin A3 and antitumor activities in Ehrlich ascites carcinoma (EAC) cell based assay. The novel purine derivatives 13a,b demonstrated potent inhibitor activities with IC50 values of 14 ± 9 and 13 ± 9 μM, respectively. Additionally, compound 15a showed the highest potency (IC50 = 10 ± 6 μM) in EAC cell based assay. Molecular modeling study, including fitting to a 3D-pharmacophore model and their docking into cyclin dependant kinase2 (CDK2) active site showed high fit values and docking scores.The manuscript describes the investigation of a series of novel purine and pyrimidine derivatives, which were prepared in good yield by using diaminomaleonitrile and tosylisocyanate in acetonitrile. Molecular modeling studies, including fitting to a 3D-pharmacophore model their docking into cycline-dependent kinase2 (CDK2) active site were performed to understand the structural features of CDK2 inhibitors. Biological evaluation for both in vitro CDK2/cyclinA3 inhibition activity and antitumor activity in Ehrlich ascites carcinoma (EAC) cell based assay were also carried out.

- by Abdel-Sattar S. Hamad Elgazwy
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- Bioinformatics, Organic Chemistry, Modeling, Cytotoxicity

The title indolo-triazolo-pyrimidines were obtained from 3-azidoindoles and can be used as models for the design of DNA-interactive compounds. Hetero-domino reaction of azidoindoles/pyrroles and acetonitriles constitutes the synthetic... more

- by Antonino Lauria
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- Organic Chemistry, Docking, Domino Reaction

Models of macromolecular assemblies are essential for a mechanistic description of cellular processes. Such models are increasingly obtained by fitting atomic-resolution structures of components into a density map of the whole assembly. Yet, current density-fitting techniques are frequently insufficient for an unambiguous determination of the positions and orientations of all components. Here, we describe MultiFit, a method for simultaneously fitting atomic structures of components into their assembly density map at resolutions as low as 25 Å. The component positions and orientations are optimized with respect to a scoring function that includes the quality-of-fit of components in the map, the protrusion of components from the map envelope, as well as the shape complementarity between pairs of components. The scoring function is optimized by our exact inference optimizer DOMINO that efficiently finds the global minimum in a discrete sampling space. MultiFit was benchmarked on 7 assemblies of known structure, consisting of up to 7 proteins each. The input atomic structures of the components were obtained from the Protein Data Bank as well as by comparative modeling based on 16-99% sequence identity to a template structure. A near-native configuration was usually found as the top-scoring model. Therefore, MultiFit can provide initial configurations for further refinement of many multi-component assembly structures described by electron microscopy.

- by Haim Wolfson
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- Algorithms, Electron Microscopy, Molecular Biology, Optimization

sakah satu contoh laporan keiatan docking kapal

- by Nina Runny
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- Molecular docking, Docking, kapal perikanan

MON 23.03  CH hatch cover sweep blast  ME Cyl. liner lack ordered gasket packing re-ordered  Plunger barrel (7pcs) ordered  Suction + puncture valves (4pcs) ordered  Boiler manometer sent for calibration  Repaired intermediate shaft t back to E/R  Re-metal int. shaft bearing arrives yard  M/E Cyl. Covers (6unit) arrives yard  M/E Piston rods (5unit) arrived yard 24.03 TUE  Apply Phillyclad to shaft liners, witnessed by class and supervised by Maker(Start : 5pm, Application-2hrs, curing 24hrs@22degC)  M/E Liners transferred to E/R  Stuffing box arrives yard  Re-assemble M/E (4unit) (Note: Yards to work OT)  A/E#1 and AE#2 kick-start and run  Winding in deck crane wire rope  FW Tanks coating arrives and start touch-up (abt. 5m2)  Leaked ballast& bilge pipe partial cut and renew  UT E/R wasted plating  Boiler hydraulic press-up WED 25.03 26.03 THU 27.03 28.03 29.03 30.03 31.03 FRI SAT SUN MON TUE 5.04 SUN TUE  Docking (early am)  M/E service engineer arrives yard  M/E Cylinder cover(2unit)arrives yard  M/E Piston rod(3unit arrives yard)  All remaining 0-Rings/packing arrives yard  Re-assemble M/E (4unit) (Note: Yards to work OT)  A/E#1 and AE#2 running  CH steel work finished  Stern plating steel work finished  CH tanks coating continued  Repair wasted bottom plating i.w.o E/R  Remaining hull plating coating started  Pressure test remaining ballast and bilge lines in double bottom tanks  Shaft alignment and fixing stern tube bearing  Docking (continued)  Kemel shaft seal engineer arrives and start works  Repair wasted bottom plating i.w.o E/R  Remaining hull plating coating continued  Repair wasted bottom plating continued  Renewal leaked ballast and bilge line  Complete re-assembling M/E  Installing tailshaft and intermediate shaft Sea Acceptance Trials  Docking/Undocking(pm)  Guangzhou Marine Automation completed works  Coating on wasted bottom plating repair completed  Complete all incomplete works planned on 25.03 to 27.03 (contingency plan)  Partial works completion report + partial final bill submitted to Owner  Cost query meeting   Docking continued  Kemel Engineer mobilize back to Singapore  Deck outfitting repairs completed  Repair wasted bottom plating completed + coating start  Renewal leaked ballast and bilge line completed  Remaining hull plating coating completed  Installing tailshaft and intermediate shaft completed  Partial works completion report + partial final bill submitted to Owner  Berthing  Rectifying defects (NK + Operational)  Container socket testing, adjusting and full weld  M/E idling run  Bow Thruster swinging test  Anchor chain lowering test  Class NK endorsed trading certificates  Cost query meeting (completed)

Non-nucleoside reverse transcriptase inhibitors (NNRTI) has a definitive role and most commonly used in treatment of HIV infection. NNRTI act by binding to specific binding site (non-nucleoside binding pocket-NNBP) in reverse transcriptase (RT) enzyme. With the objective of developing efficient NNRTI, we have designed various Isatin analogs for effective treatment of AIDS and were subjected to molecular docking studies on five different crystal structures of RT complexed with five different ligands Nevirapine, Delaviridine, Efavirenz, Etravirine, and Rilpivirine. Combined dock-score of compound N21, N11, N23 was found to be comparable with standards indicated that Isatin analogs have good binding affinity for NNBP. Docking results suggested that these types of compounds could be binding in the NNRTI binding site in a similar mode to a known non-nucleoside inhibitors. ADME properties of Isatin analogs were also analyzed using Qikprop 2.5 tool of Schrodinger software.

- by Deepak Lokwani
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- Medicinal Chemistry, Crystal structure, Molecular docking, Hiv Infection

In untraditional environments and unexpected situations, it is not always possible for a fixed-architecture robot to meet all the task requirements. Self-assembly enables free bodies to autonomously join together and complete a task that would otherwise not be achievable with the independent modules. The main theme of this thesis is to investigate the possibility of converting frail and inflexible mobile robots to a single flexible modular robot, and conversely, to split up a long and slow structure into separate fast modules. To prove the possibility of having such a system, we propose a novel connection mechanism, as well as a vision-based docking guidance system. This docking system along with a parking control algorithm allow single articulated- steering mobile robots to autonomously connect and disconnect. So, the concept of this work lies at the intersection between modular and wheeled mobile robotic systems. The goal is to improve the performance of mobile robots by autonomously changing their locomotion method to best fit the terrain conditions

- by Mehdi Delrobaei
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- Localization, Lyapunov Stability Theory, Docking, Visual navigation

Resumen Context: Nyctanthes arbor-tristis L. (Oleaceae) leaf are used in treatment of malaria, rheumatoid arthritis, chronic fever and enlargement of spleen; however, there is paucity of information on its hepatoprotective and antioxidant potential. Aims: To evaluate hepatoprotective and antioxidant potentials of ethanolic leaf extract of Nyctanthes arbor-tristis L. Methods: After collection and authentication of the vegetal material, ethanolic extract was collected. The combination of antitubercular drugs (isoniazid, rifampicin and pyrazinamide) was used to induce hepatotoxicity in Wistar rats. Hepatoprotective effect was evaluated at doses 125, 250 and 500 mg/kg, body weight by estimating the activities of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and levels of total bilirubin (TBL). The effects on lipid peroxidation (LPO), reduced glutathione (GSH) and catalase (CAT), superoxide dismutase (SOD) were estimated. Docking study was conducted to anticipate the probable biological targets associated with its hepatoprotective effect. Results: The plant extract dose of 500 mg/kg, body weight significantly declined the levels of AST, ALT, ALP and TBL at (p < 0.001), which is approximately corresponding to the dose of reference compound silymarin and reversed the levels of LPO, GSH, SOD, CAT as compared to silymarin dose. Histopathological studies revealed regeneration of hepatocytes. The docking results suggested that some active constituents of plant leaves potentially interact with human pregnane X receptor, human constitutive androstane receptor and the farnesoid X receptor. Conclusions: The extract of Nyctanthes arbor-tristis L. remarkably possesses hepatoprotective and antioxidant effect and evinced its traditional claim. Future studies should be done to isolate active phytoconstituents for use in drug discovery.

- by Engr. Khairulmuzammil YUZRI
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- Docking

The reaction of o-phenylene diamine and ethyl oxamate is reinvestigated and led to 3-aminoquinoxalin-2(1H)-one rather than benzimidazole-2-carboxamide as was previously reported. The structure of the obtained quinoxaline has been confirmed by X-ray. The anti-tumor activity of synthesized quinoxalines 1–21 has been evaluated by studying their possible inhibitory effects on Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Among the studied compounds 1–21, compounds 12, 8, 13, 18, 17 and 19, respectively, demonstrated strong inhibitory effects on the EBV-EA activation without showing any cytotoxicity and their effects being stronger than that of a representative control, oleanolic acid. Furthermore, compound 12 exhibited a remarkable inhibitory effect on skin tumor promotion in an in vivo two-stage mouse skin carcinogenesis test using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter. The result of the present investigation indicated that compound 12 might be valuable as a potent cancer chemopreventive agent. Moreover, the molecular docking into PTK (PDB: 1t46) has been done for lead optimization of the aforementioned compounds as potential PTK inhibitors.Ligand interaction and the binding mode of compound 17 with c-kit receptor, it exhibited 3 H-bonds with the amino acids in C-kit two of them with CYS 673 and one with ASP 677, the hydrogen bonds formed colored in green.► New quinoxalines derivatives have been synthesized to evaluate their cancer chemopreventive activity. ► The inhibitory effects of compounds 1–21 on Epsteine Barr virus early antigen (EBV-EA) activation induced by TPA have been studied. ► The in vivo two-stage carcinogenesis test of compound 12 was studied. ► The synthesized compounds docked into c-kit protein-tyrosine kinase.

- by mona atta
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- Organic Chemistry, Modeling, Signal Transduction, X Rays

Vinblastine (VLB), a cytotoxic alkaloid is used extensively against various cancer types and the crystal structure of its tubulin complex is already known. Multitarget affinity of vinblastine has been investigated and the nature of binding with biological receptors namely, duplex DNA and Human serum albumin (HSA) has been compared to the binding characteristics of its known complex with natural high affinity receptor tubulin using molecular docking and QM–MM calculations. VLB is found to interact with DNA as well as HSA protein, though, with weaker affinity as compared to tubulin. Analysis of various docked complexes revealed that the H-bonds and cation–pi bonds do not have significant contribution to the binding interactions and despite its large size, VLB remains in relaxed conformation and fits in the hydrophobic regions on the receptors.

- by Prateek Pandya
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- Molecular Recognition, Anticancer Drugs, Docking, ONIOM

The research was conducted by in silico screening of Angiotensin-I Converting Enzyme (ACE) inhibitors from Roselle (Hibiscus sabdariffa) chemical compounds. The objective research was to determine the active compounds Roselle (Hibiscus sabdariffa) as a potential inhibitor of Angiotensin-I Converting Enzyme (ACE) by using in silico screening method.The research was conducted using chemical compounds Roselle (Hibiscus sabdariffa) downloaded via Take Out "Jamu" Knapsack and models of Angiotensin-I Converting Enzyme downloaded via Protein Data Bank (PDB) with code 1O86, then performed docking process using the PyRx program, and then evaluated of the free energy (ΔG) as docking process results. Result show that 3 of the Roselle (Hibiscus sabdariffa) chemical compounds have the lowest free energy value and potential as inhibitors of Angiotensin-I Converting Enzyme better than Lisinopril. Those are Hibiscetin, Hibiscetin 3-glucoside, and delphinidin 3-sambubioside with free energy (ΔG) are respectively -8.1 kcal / mol, -9.1 kcal / mol and -9.4 kcal / mol.

- by Dewi Yuliana
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- Pharmacology, Biochemistry, Pharmacy, Toxicology

Over time due to increase in knowledge and technology, researchers, scientists and pharmacologists have witnessed a dramatic development in the area of drug design and drug development. As is the case with any given drug, side effects are unavoidable. To control the levels of these side effects, controlled drug delivery systems have been developed. Drug delivery system using nanoparticles is a novel approach for controlled delivery of drugs. The main advantage in using nanoparticles is that they are found to protect the pharmacological properties of the drug, prevent the pharmacological active substances from degradation during storage and early degradation/inactivation including controlled release of the drug.

- by Christina Rekha
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- Docking, Doxorubicin, Human Serum Albumin (HSA)