Faez I Khan | Xi'an Jiaotong-Liverpool University (original) (raw)
Papers by Faez I Khan
Frontiers in chemistry, Jun 24, 2024
Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer ma... more Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer management, volume II Cancer, one of the leading causes of death worldwide, remains a serious public health concern. Even with significant advances in drug discovery, developing novel and useful small-molecule drugs remains a difficult, costly, and time-consuming process that necessitates the collaboration of numerous experts in interdisciplinary domains such as drug metabolism, computational biology, and clinical research. Computational approaches in drug discovery are crucial and in high demand, significantly impacting time and cost savings while increasing efficiency. Computational approaches, such as molecular docking, molecular dynamics simulations, pharmacophore modeling, and QSAR, are efficient tools for gaining insights into the structure-function relationships of small molecules and medicinal compounds with target proteins. These methods are widely used in the identification and optimization of lead compounds. The key objectives of the drug discovery process are to identify potential toxicity, predict the metabolic fate of a drug candidate, and establish a connection between pharmacodynamics and pharmacokinetics. Recent advancements in in silico techniques have enabled researchers to collect more reliable data. Additionally, the rise of AI and deep learning in drug discovery is revolutionizing the field, significantly impacting the discovery of new molecules for various diseases, including cancer. Researchers were interested in this Research Topic, and many manuscripts were submitted. Six Original Research articles that explain advanced in silico techniques relevant to the drug discovery domain and span a broad spectrum of CADD topics have been published out of these submissions. A brief overview of the articles that have been published is as follows: Rahaman et al. investigated the mechanism of plumbagin's (PLM) binding to calf thymus DNA. UV-Vis spectroscopy indicated that PLM binds to ctDNA, and dye displacement assays confirmed the formation of PLM-ctDNA complex. PLM has little
Objective: Neuropathic pain (NP) is defined as pain associated with damage or permanent alteratio... more Objective: Neuropathic pain (NP) is defined as pain associated with damage or permanent alteration of the peripheral or central nervous system. Current drug treatment for the management of neuropathic pain associated with various adverse effects. The present study was designed to investigate the combined effect of acamprosate and baclofen in experimental model of peripheral neuropathic pain in wistar rats. Material and methods: Neuropathic pain was induced by Chronic constriction injured (CCI) of sciatic nerve in rats. Acamprosate (100 and 200 mg/kg p.o) and baclofen (10 and 20 mg/kg p.o) was given in different groups for 14 days starting on 7th day post sciatic nerve ligation. Further combination of acamprosate(100 mg/kg p.o) and baclofen (10 mg/kg p.o) was also given to one group. On 1th, 3rd, 7th, 14thand 21stday behavioral parameters like mechanical allodynia and thermal hyperalgesia were assessed. Then animals were sacrificed on 22nd day and biochemical parameters (GSH, LPO, ca...
Frontiers in Chemistry, Dec 6, 2023
Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer ma... more Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer management Cancer remains a major public health concern, with it ranking as the leading cause of death worldwide. Despite significant advances in biotechnology, developing practical and innovative small-molecule drugs remains a hard, time-consuming, and costly process. This endeavor necessitates the collaboration of experts from a variety of disciplines, including computational biology, drug metabolism, and clinical research. Hence, there is a pressing need for novel drug development processes that save time and cost while improving overall efficiency. Computer-aided drug design (CADD) methodologies are becoming increasingly crucial in drug discovery, particularly in their ability to identify promising drug candidates cost-effectively. In this area of study, we launched a Research Topic in Frontiers in Chemistry journal titled "Computational Drug Discovery of Medicinal Compounds for Cancer Management." This Research Topic attracted the interest of researchers, and a large number of manuscripts were submitted. Among these submissions, 15 Original Research articles have been published covering a wide range of CADD topics and elucidating advanced in silico methodologies applicable to the field of drug discovery. The following is a summary of the published articles: Dain Md Opo et al. used structure-based pharmacophore modeling and virtual screening to identify potentially natural lead compounds that can inhibit BRAF and thus inhibiting cancer. Promising candidate compounds targeting the upregulated BRAF gene have been identified using in silico drug design methodologies and computational tools. The study identified four potential compounds by utilizing these computational methods. The investigation suggests that these compounds may be useful against a range of cancers by specifically targeting the overexpressed BRAF gene. Ashraf et al. presented a comprehensive study on potential inhibitors of Tyrosine Threonine Kinase (TTK), a target in a variety of human cancers including breast,
International Journal of Molecular Sciences, Jun 26, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy
Journal of Molecular Recognition
Various spectroscopic techniques involving fluorescence spectroscopy, circular dichroism (CD), an... more Various spectroscopic techniques involving fluorescence spectroscopy, circular dichroism (CD), and computational approaches were used to elucidate the molecular aspects of interaction between the antiepileptic drug topiramate and the multifunctional transport protein bovine serum albumin (BSA) under physiological conditions. Topiramate quenched BSA fluorescence in a static quenching mode, according to the Stern‐Volmer quenching constant (Ksv) data derived from fluorescence spectroscopy for the topiramate‐BSA complex. The binding constant was also used to calculate the binding affinity for the topiramate‐BSA interaction. Fluorescence and circular dichroism experiments demonstrate that the protein's tertiary structure is affected by the microenvironmental alterations generated by topiramate binding to BSA. To establish the exact binding site, interacting residues, and interaction forces involved in the binding of topiramate to BSA, molecular modeling and simulation approaches were...
Journal of Biomolecular Structure and Dynamics, 2021
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal l... more Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal loss to human health and lives and has deeply impacted socio-economic growth. Remarkable efforts have been made by the scientific community in containing the virus by successful development of vaccines and diagnostic kits. Initiatives towards drug repurposing and discovery have also been undertaken. In this study, we compiled the known natural anti-viral compounds using text mining of the literature and examined them against four major structural proteins of SARS-CoV-2, namely, spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. Following computational approaches, we identified fangchinoline and versicolactone C as the compounds to exhibit strong binding to the target proteins and causing structural deformation of three structural proteins (N, S and M). We recommend the inhibitory effects of these compounds from our study should be experimentally validated against SARS-CoV-2. Communicated by Ramaswamy H. Sarma
Bioorganic Chemistry, 2021
N-formyl pyrazoline derivatives (3a-3l) were designed and synthesized via Michael addition reacti... more N-formyl pyrazoline derivatives (3a-3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV-visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a-3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a-3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure-function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a-3l) was examined by relaxation assay at varying concentrations 100-1000 µM.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2021
A photoactivatable near-infrared fluorescent protein (NIR-FP) PAiRFP1 has been developed by 15 am... more A photoactivatable near-infrared fluorescent protein (NIR-FP) PAiRFP1 has been developed by 15 amino acid substitutions in its nonfluorescent template Agp2. In our previous communication, we investigated the role of three amino acids in PHY domain distal from BV molecule. The impact of the twelve amino acids in GAF domain, especially five residues near BV-binding pocket is unclear. In this paper, PCR based reverse mutagenesis, spectroscopic methods, molecular modelling and simulations have been employed to explore the roles of these substitutions during the molecular evolution of PAiRFP1. It was found that the residue L163 is important for protein folding in PAiRFP1. The residues F244 and C280 exerted remarkable effects on molar extinction coefficient, NIR fluorescence quantum yield, molecular brightness, fluorescence fold, and dark recovery rate. The residues F244 and V276 modulate the maximum absorption and emission peak position. The reverse mutant L168M exhibited a higher fluorescence fold than PAiRFP1. Additionally, the reverse mutants V203A, V294E, S218G and D127G possessed better spectral properties than PAiRFP1. This study is important for the rational design of a better BphP-based photoactivatable NIR-FPs.
International Journal of Biological Macromolecules, 2020
Process Biochemistry, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019
International Journal of Biological Macromolecules, 2019
Protein misfolding diseases are associated with human pathologies. These neurodegenerative diseas... more Protein misfolding diseases are associated with human pathologies. These neurodegenerative diseases remain challenging task for researchers because of their adverse effect on vital organs system. Lysozyme amyloidosis is also associated with multi-organ dysfunction. Hence elucidation of its folding pathway is of great importance, for which hen egg white lysozyme (HEWL) being homological to its human counterpart was taken into consideration. Here in this study we have investigated the effect of diosmin (DSN), a flavonoid over thermally aggregated HEWL. Decrease in ANS, ThT and Rayleigh scattering fluorescence intensity suggests the transition between β to α conformations. Further decrease in absorbance at 360 nm and of congo red with slight blue shift also indicated the disappearance of β sheeted structure under the under the influence of increasing concentration of DSN. These results were also supported by circular dichroism in which gradual appearance α helical structure was observed. Finally visualization under transmission electron microscopy (TEM) authenticated the maximum structural alteration in the previously formed aggregates of HEWL at 250 μM DSN. Molecular docking followed by 100 ns MD simulations help to understand the interaction mechanism of HEWL with DSN. Results suggest DSN could be a useful in the treatment of amyloid related disorders.
International Journal of Antimicrobial Agents, 2018
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights Leishmania donovani pyruvate phosphate dikinase was explored for new drug target Structure based drug designing and homology modelling was performed Virtual screening and molecular dynamics of ZINC data base was carried out Identification and characterization of a novel inhibitor Z220582104 Leishmanicidal effects of Z220582104 against the parasite was investigated
Current Protein & Peptide Science, 2018
Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Ridley a... more Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Ridley and Jopling classified the disease into five polar forms, Tuberculoid (TT) and Lepromatous (LL), in between two forms of the disease Borderline tuberculoid (BT), Borderline (BB) and Borderline lepromatous (BL) are laid. The tuberculoid type (BT/TT) leprosy patients show good recall of cell-mediated immune (CMI) response and Th1 type of immune response, while lepromatous leprosy (LL) patients show defect in cell-mediated immunity to the causative agent and Th2 type of immune response. Due to distinct clinical and immunological spectra of the disease, leprosy attracted immunologists to consider an ideal model for the study of deregulations of various immune reactions. Recent studies show that Tregs, Th3 (TGF-β, IL-10), IL-35 producing Treg immune response associated with the immune suppressive environment, survival of bugs and associated with lepromatous leprosy. IL-17 producing Th17 immune response associated with tuberculoid leprosy and play protective role. γδ T cells also increased from tuberculoid to lepromatous pole of leprosy. In this review, we will discuss the role of various subtypes of T-cell and their cytokines in the pathogenesis of leprosy.
Journal of Molecular Catalysis B: Enzymatic, 2017
Highlights SMG1-F278D was studied for the production of DAG. SMG1-F278D exhibited 4-fold increase... more Highlights SMG1-F278D was studied for the production of DAG. SMG1-F278D exhibited 4-fold increased esterification activity as well as superior FA specificity towards medium chain FAs. Molecular docking suggested that caprylic acid strongly bound to the catalytic pocket of SMG1-F278D. MD simulations suggested the stable nature of SMG1-F278D due to increase in β-sheet and α-helix. Further, the esterification process for the production of DAG was optimized. Diacylglycerol production by genetically modified lipase from Malassezia globosa
International Journal of Biological Macromolecules, 2016
Cyanobacterial phycoerythrin (αC-PE) from Phormidium tenue exists in two natural forms named as f... more Cyanobacterial phycoerythrin (αC-PE) from Phormidium tenue exists in two natural forms named as full length (FL-αC-PE) and truncated (Tr-αC-PE). FL-αC-PE and Tr-αC-PE are produced when cyanobacterium is grown in the optimal medium and nutrient deficient medium, respectively. Despite of N-terminal deletion, both proteins show similar spectroscopic properties. In this study, different optical properties of these two natural variants of C-PE were measured in the pH range 1.0-12.0 (1.0≤pH≤12.0). It was observed that: (i) their absorption, fluorescence and CD spectra remain unchanged within the range adjacent to neutral pH, 5.5-8.75, (ii) at pH values higher than 8.75 and lower than 5.5 their absorption, fluorescence and CD spectral signatures are changed significantly, and (iii) emission spectra of the covalently linked tetrapyrrole chromophores and Trp residue are perturbed at extreme pH values in the range 8.75<pH<5.5. Refolding experiments further suggest that pH-induced denaturation of both forms of C-PE is reversible in the pH range 2.5-11.0, but irreversible beyond this range on both sides of pH extremes. The pH-induced denaturation of both the full length and truncated αC-PEs follows a two-state mechanism.
Frontiers in chemistry, Jun 24, 2024
Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer ma... more Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer management, volume II Cancer, one of the leading causes of death worldwide, remains a serious public health concern. Even with significant advances in drug discovery, developing novel and useful small-molecule drugs remains a difficult, costly, and time-consuming process that necessitates the collaboration of numerous experts in interdisciplinary domains such as drug metabolism, computational biology, and clinical research. Computational approaches in drug discovery are crucial and in high demand, significantly impacting time and cost savings while increasing efficiency. Computational approaches, such as molecular docking, molecular dynamics simulations, pharmacophore modeling, and QSAR, are efficient tools for gaining insights into the structure-function relationships of small molecules and medicinal compounds with target proteins. These methods are widely used in the identification and optimization of lead compounds. The key objectives of the drug discovery process are to identify potential toxicity, predict the metabolic fate of a drug candidate, and establish a connection between pharmacodynamics and pharmacokinetics. Recent advancements in in silico techniques have enabled researchers to collect more reliable data. Additionally, the rise of AI and deep learning in drug discovery is revolutionizing the field, significantly impacting the discovery of new molecules for various diseases, including cancer. Researchers were interested in this Research Topic, and many manuscripts were submitted. Six Original Research articles that explain advanced in silico techniques relevant to the drug discovery domain and span a broad spectrum of CADD topics have been published out of these submissions. A brief overview of the articles that have been published is as follows: Rahaman et al. investigated the mechanism of plumbagin's (PLM) binding to calf thymus DNA. UV-Vis spectroscopy indicated that PLM binds to ctDNA, and dye displacement assays confirmed the formation of PLM-ctDNA complex. PLM has little
Objective: Neuropathic pain (NP) is defined as pain associated with damage or permanent alteratio... more Objective: Neuropathic pain (NP) is defined as pain associated with damage or permanent alteration of the peripheral or central nervous system. Current drug treatment for the management of neuropathic pain associated with various adverse effects. The present study was designed to investigate the combined effect of acamprosate and baclofen in experimental model of peripheral neuropathic pain in wistar rats. Material and methods: Neuropathic pain was induced by Chronic constriction injured (CCI) of sciatic nerve in rats. Acamprosate (100 and 200 mg/kg p.o) and baclofen (10 and 20 mg/kg p.o) was given in different groups for 14 days starting on 7th day post sciatic nerve ligation. Further combination of acamprosate(100 mg/kg p.o) and baclofen (10 mg/kg p.o) was also given to one group. On 1th, 3rd, 7th, 14thand 21stday behavioral parameters like mechanical allodynia and thermal hyperalgesia were assessed. Then animals were sacrificed on 22nd day and biochemical parameters (GSH, LPO, ca...
Frontiers in Chemistry, Dec 6, 2023
Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer ma... more Editorial on the Research Topic Computational drug discovery of medicinal compounds for cancer management Cancer remains a major public health concern, with it ranking as the leading cause of death worldwide. Despite significant advances in biotechnology, developing practical and innovative small-molecule drugs remains a hard, time-consuming, and costly process. This endeavor necessitates the collaboration of experts from a variety of disciplines, including computational biology, drug metabolism, and clinical research. Hence, there is a pressing need for novel drug development processes that save time and cost while improving overall efficiency. Computer-aided drug design (CADD) methodologies are becoming increasingly crucial in drug discovery, particularly in their ability to identify promising drug candidates cost-effectively. In this area of study, we launched a Research Topic in Frontiers in Chemistry journal titled "Computational Drug Discovery of Medicinal Compounds for Cancer Management." This Research Topic attracted the interest of researchers, and a large number of manuscripts were submitted. Among these submissions, 15 Original Research articles have been published covering a wide range of CADD topics and elucidating advanced in silico methodologies applicable to the field of drug discovery. The following is a summary of the published articles: Dain Md Opo et al. used structure-based pharmacophore modeling and virtual screening to identify potentially natural lead compounds that can inhibit BRAF and thus inhibiting cancer. Promising candidate compounds targeting the upregulated BRAF gene have been identified using in silico drug design methodologies and computational tools. The study identified four potential compounds by utilizing these computational methods. The investigation suggests that these compounds may be useful against a range of cancers by specifically targeting the overexpressed BRAF gene. Ashraf et al. presented a comprehensive study on potential inhibitors of Tyrosine Threonine Kinase (TTK), a target in a variety of human cancers including breast,
International Journal of Molecular Sciences, Jun 26, 2023
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy
Journal of Molecular Recognition
Various spectroscopic techniques involving fluorescence spectroscopy, circular dichroism (CD), an... more Various spectroscopic techniques involving fluorescence spectroscopy, circular dichroism (CD), and computational approaches were used to elucidate the molecular aspects of interaction between the antiepileptic drug topiramate and the multifunctional transport protein bovine serum albumin (BSA) under physiological conditions. Topiramate quenched BSA fluorescence in a static quenching mode, according to the Stern‐Volmer quenching constant (Ksv) data derived from fluorescence spectroscopy for the topiramate‐BSA complex. The binding constant was also used to calculate the binding affinity for the topiramate‐BSA interaction. Fluorescence and circular dichroism experiments demonstrate that the protein's tertiary structure is affected by the microenvironmental alterations generated by topiramate binding to BSA. To establish the exact binding site, interacting residues, and interaction forces involved in the binding of topiramate to BSA, molecular modeling and simulation approaches were...
Journal of Biomolecular Structure and Dynamics, 2021
Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal l... more Abstract The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a colossal loss to human health and lives and has deeply impacted socio-economic growth. Remarkable efforts have been made by the scientific community in containing the virus by successful development of vaccines and diagnostic kits. Initiatives towards drug repurposing and discovery have also been undertaken. In this study, we compiled the known natural anti-viral compounds using text mining of the literature and examined them against four major structural proteins of SARS-CoV-2, namely, spike (S) protein, nucleocapsid (N) protein, membrane (M) protein and envelope (E) protein. Following computational approaches, we identified fangchinoline and versicolactone C as the compounds to exhibit strong binding to the target proteins and causing structural deformation of three structural proteins (N, S and M). We recommend the inhibitory effects of these compounds from our study should be experimentally validated against SARS-CoV-2. Communicated by Ramaswamy H. Sarma
Bioorganic Chemistry, 2021
N-formyl pyrazoline derivatives (3a-3l) were designed and synthesized via Michael addition reacti... more N-formyl pyrazoline derivatives (3a-3l) were designed and synthesized via Michael addition reaction through cyclization of chalcones with hydrazine hydrate in presence of formic acid. The structural elucidation of N-formyl pyrazoline derivatives was carried out by various spectroscopic techniques such as 1H, 13C NMR, FT-IR, UV-visible spectroscopy, mass spectrometry and elemental analysis. Anticancer activity of the pyrazoline derivatives (3a-3l) was evaluated against human lung cancer (A549), fibrosarcoma cell lines (HT1080) and human primary normal lung cells (HFL-1) by MTT assay. The results of anticancer activity showed that potent analogs 3b and 3d exhibited promising activity against A549 (IC50 = 12.47 ± 1.08 and 14.46 ± 2.76 µM) and HT1080 (IC50 = 11.40 ± 0.66 and 23.74 ± 13.30 µM) but low toxic against the HFL-1 (IC50 = 116.47 ± 43.38 and 152.36 ± 22.18 µM). The anticancer activity of potent derivatives (3b and 3d) against A549 cancer cell line was further confirmed by flow cytometry based approach. DNA binding interactions of the pyrazoline derivatives 3b and 3d have been carried out with calf thymus DNA (Ct-DNA) using absorption, fluorescence and viscosity measurements, circular dichroism and cyclic voltammetry. Antioxidant potential of N-formyl pyrazoline derivatives (3a-3l) has been also estimated through DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical and H2O2. Results revealed that all the compounds exhibited significant antioxidant activity. In silico molecular modelling and ADMET properties of pyrazoline derivatives were also studied using PyRx software against topoisomerase II receptor with PDB ID: 1ZXM to explore their best hits. MD simulation of 3b and 3d was also carried out with topoisomerase II for structure-function correlation in a protein. HuTopoII inhibitory activity of the analogs (3a-3l) was examined by relaxation assay at varying concentrations 100-1000 µM.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2021
A photoactivatable near-infrared fluorescent protein (NIR-FP) PAiRFP1 has been developed by 15 am... more A photoactivatable near-infrared fluorescent protein (NIR-FP) PAiRFP1 has been developed by 15 amino acid substitutions in its nonfluorescent template Agp2. In our previous communication, we investigated the role of three amino acids in PHY domain distal from BV molecule. The impact of the twelve amino acids in GAF domain, especially five residues near BV-binding pocket is unclear. In this paper, PCR based reverse mutagenesis, spectroscopic methods, molecular modelling and simulations have been employed to explore the roles of these substitutions during the molecular evolution of PAiRFP1. It was found that the residue L163 is important for protein folding in PAiRFP1. The residues F244 and C280 exerted remarkable effects on molar extinction coefficient, NIR fluorescence quantum yield, molecular brightness, fluorescence fold, and dark recovery rate. The residues F244 and V276 modulate the maximum absorption and emission peak position. The reverse mutant L168M exhibited a higher fluorescence fold than PAiRFP1. Additionally, the reverse mutants V203A, V294E, S218G and D127G possessed better spectral properties than PAiRFP1. This study is important for the rational design of a better BphP-based photoactivatable NIR-FPs.
International Journal of Biological Macromolecules, 2020
Process Biochemistry, 2019
This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 2019
International Journal of Biological Macromolecules, 2019
Protein misfolding diseases are associated with human pathologies. These neurodegenerative diseas... more Protein misfolding diseases are associated with human pathologies. These neurodegenerative diseases remain challenging task for researchers because of their adverse effect on vital organs system. Lysozyme amyloidosis is also associated with multi-organ dysfunction. Hence elucidation of its folding pathway is of great importance, for which hen egg white lysozyme (HEWL) being homological to its human counterpart was taken into consideration. Here in this study we have investigated the effect of diosmin (DSN), a flavonoid over thermally aggregated HEWL. Decrease in ANS, ThT and Rayleigh scattering fluorescence intensity suggests the transition between β to α conformations. Further decrease in absorbance at 360 nm and of congo red with slight blue shift also indicated the disappearance of β sheeted structure under the under the influence of increasing concentration of DSN. These results were also supported by circular dichroism in which gradual appearance α helical structure was observed. Finally visualization under transmission electron microscopy (TEM) authenticated the maximum structural alteration in the previously formed aggregates of HEWL at 250 μM DSN. Molecular docking followed by 100 ns MD simulations help to understand the interaction mechanism of HEWL with DSN. Results suggest DSN could be a useful in the treatment of amyloid related disorders.
International Journal of Antimicrobial Agents, 2018
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service... more This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Highlights Leishmania donovani pyruvate phosphate dikinase was explored for new drug target Structure based drug designing and homology modelling was performed Virtual screening and molecular dynamics of ZINC data base was carried out Identification and characterization of a novel inhibitor Z220582104 Leishmanicidal effects of Z220582104 against the parasite was investigated
Current Protein & Peptide Science, 2018
Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Ridley a... more Leprosy is an infectious disease caused by non-cultivable bacteria Mycobacterium leprae. Ridley and Jopling classified the disease into five polar forms, Tuberculoid (TT) and Lepromatous (LL), in between two forms of the disease Borderline tuberculoid (BT), Borderline (BB) and Borderline lepromatous (BL) are laid. The tuberculoid type (BT/TT) leprosy patients show good recall of cell-mediated immune (CMI) response and Th1 type of immune response, while lepromatous leprosy (LL) patients show defect in cell-mediated immunity to the causative agent and Th2 type of immune response. Due to distinct clinical and immunological spectra of the disease, leprosy attracted immunologists to consider an ideal model for the study of deregulations of various immune reactions. Recent studies show that Tregs, Th3 (TGF-β, IL-10), IL-35 producing Treg immune response associated with the immune suppressive environment, survival of bugs and associated with lepromatous leprosy. IL-17 producing Th17 immune response associated with tuberculoid leprosy and play protective role. γδ T cells also increased from tuberculoid to lepromatous pole of leprosy. In this review, we will discuss the role of various subtypes of T-cell and their cytokines in the pathogenesis of leprosy.
Journal of Molecular Catalysis B: Enzymatic, 2017
Highlights SMG1-F278D was studied for the production of DAG. SMG1-F278D exhibited 4-fold increase... more Highlights SMG1-F278D was studied for the production of DAG. SMG1-F278D exhibited 4-fold increased esterification activity as well as superior FA specificity towards medium chain FAs. Molecular docking suggested that caprylic acid strongly bound to the catalytic pocket of SMG1-F278D. MD simulations suggested the stable nature of SMG1-F278D due to increase in β-sheet and α-helix. Further, the esterification process for the production of DAG was optimized. Diacylglycerol production by genetically modified lipase from Malassezia globosa
International Journal of Biological Macromolecules, 2016
Cyanobacterial phycoerythrin (αC-PE) from Phormidium tenue exists in two natural forms named as f... more Cyanobacterial phycoerythrin (αC-PE) from Phormidium tenue exists in two natural forms named as full length (FL-αC-PE) and truncated (Tr-αC-PE). FL-αC-PE and Tr-αC-PE are produced when cyanobacterium is grown in the optimal medium and nutrient deficient medium, respectively. Despite of N-terminal deletion, both proteins show similar spectroscopic properties. In this study, different optical properties of these two natural variants of C-PE were measured in the pH range 1.0-12.0 (1.0≤pH≤12.0). It was observed that: (i) their absorption, fluorescence and CD spectra remain unchanged within the range adjacent to neutral pH, 5.5-8.75, (ii) at pH values higher than 8.75 and lower than 5.5 their absorption, fluorescence and CD spectral signatures are changed significantly, and (iii) emission spectra of the covalently linked tetrapyrrole chromophores and Trp residue are perturbed at extreme pH values in the range 8.75<pH<5.5. Refolding experiments further suggest that pH-induced denaturation of both forms of C-PE is reversible in the pH range 2.5-11.0, but irreversible beyond this range on both sides of pH extremes. The pH-induced denaturation of both the full length and truncated αC-PEs follows a two-state mechanism.