Computational Virtual Screening Towards Designing Novel Anticancer Drugs (original) (raw)

MOLECULAR DOCKING: AN EXPLANATORY APPROACH IN STRUCTURE-BASED DRUG DESIGNING AND DISCOVERY Review Article

International Journal of Pharmacy and Pharmaceutical Sciences, 2021

Molecular docking is a modeling tool of Bioinformatics which includes two or more molecules which interact to provide a stable product in the form of a complex. Molecular docking is helpful in predicting the 3-d structure of a complex which depends on the binding characteristics of Ligand and target. Also, it is a structure-based virtual screening (SBVS) utilized to keep the 3-d structures of small molecule which are generated by computers into a target structure in various types of conformations, positions and orientations. This molecular docking has come out to be a novel concept with various types of advantages. It behaves as a highly exploring domain due to its significant structure-based drug design (SBDD), Assessment of Biochemical pathways, Lead Optimization and in De Novo drug design. In spite of all potential approaches, there are certain challenges which arescoring function (differentiate the true binding mode), ligand chemistry (tautomerism and ionization) and receptor flexibility (single conformation of rigid receptor). The area of computer-aided drug design and discovery (CADDD) has achieved large favorable outcomes in the past few years. CADD has been adopted by various big pharmaceutical companies for leading discoveries of drugs. Many researchers have worked in order to examine different docking algorithms and to predict molecules' active site. Hence, this Review article depicts the whole sole of Molecular Docking.

Structure-Based Drug Design: Docking and Scoring

This review gives an introduction into ligand -receptor docking and illustrates the basic underlying concepts. An overview of different approaches and algorithms is provided. Although the application of docking and scoring has led to some remarkable successes, there are still some major challenges ahead, which are outlined here as well. Approaches to address some of these challenges and the latest developments in the area are presented. Some aspects of the assessment of docking program performance are discussed. A number of successful applications of structure-based virtual screening are described.

Molecular Docking: An Explanatory Approach in Structure-Based Drug Designing and Discovery

International Journal of Pharmacy and Pharmaceutical Sciences, 2021

Molecular docking is a modeling tool of bioinformatics which includes two or more molecules which interact to provide a stable product in the form of a complex. Molecular docking is helpful in predicting the 3-d structure of a complex which depends on the binding characteristics of ligand and target. Also, it is a structure-based virtual screening (SBVS) utilized to keep the 3-d structures of small molecules which are generated by computer into a target structure in various types of conformations, positions and orientations. This molecular docking has come out to be a novel concept with various types of advantages. It behaves as a highly exploring domain due to its significant structure-based drug design (SBDD), Assessment of Biochemical pathways, Lead Optimization and in De Novo drug design. In spite of all potential approaches there are certain challenges which are-scoring function (differentiate true binding mode), ligand chemistry (tautomerism and ionization) and receptor flexib...

Docking and scoring in virtual screening for drug discovery: methods and applications

Nature Reviews Drug Discovery, 2004

| Computational approaches that 'dock' small molecules into the structures of macromolecular targets and 'score' their potential complementarity to binding sites are widely used in hit identification and lead optimization. Indeed, there are now a number of drugs whose development was heavily influenced by or based on structure-based design and screening strategies, such as HIV protease inhibitors. Nevertheless, there remain significant challenges in the application of these approaches, in particular in relation to current scoring schemes. Here, we review key concepts and specific features of small-molecule-protein docking methods, highlight selected applications and discuss recent advances that aim to address the acknowledged limitations of established approaches.

A review of approaches in computer-aided drug design in drug discovery

GSC Biological and Pharmaceutical Sciences

The process of discovering and developing a new medication is often seen as a lengthy and expensive endeavors. As a result, computer-aided drug design methods are now frequently utilized to improve the efficiency of the drug discovery and development process. Various CADD approaches are regarded as potential techniques based on their needs; nevertheless, structure-based drug design and ligand-based drug design approaches are well-known as highly efficient and powerful strategies in drug discovery and development. Both of these approaches may be used in conjunction with molecular docking to conduct virtual screening for the purpose of identifying and optimizing leads. In recent years, computational tools have become increasingly popular in the pharmaceutical industry and academic fields as a means of improving the efficiency and effectiveness of the drug discovery and development pipeline. In this post, we'll go over computational methods, which are a creative way of discovering ...

Virtual screening strategies in drug design–methods and applications

Biotechnologia, 2011

Virtual screening (VS) overcomes the limitations of traditional high-throughput screening (HTS) by applying computer-based methods in drug discovery. VS takes advantage of fast algorithms to filter chemical space and successfully select potential drug candidates. A key aspect in structure-based VS is the sampling of ligand-receptor conformations and the evaluation of these poses to predict near-native binding modes. The development of fast and accurate algorithms during the last few years has allowed VS to become an important tool in drug discovery and design. Herein, an overview of widely used ligand-based (e.g., similarity, pharmacophore searches) and structure-based (protein-ligand docking) VS methods is discussed. Their strengths and limitations are described, along with many successful stories. This review not only serves as an introductory guide for inexperienced VS users but also presents a general overview of the current state and scope of these powerful tools.

Docking, virtual high throughput screening and in silico fragment-based drug design

Journal of Cellular and Molecular Medicine, 2009

The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high-throughput screening and fragment-based ligand design.

Molecular Docking in Drug Discovery

Journal of Pharmaceutical Research, 2021

In last few years the Computer Aided Drug Design and Discovery is many success rates. In academics and many pharmaceutical industries for drug lead discovery they adopt the Computational Drug Design. The modern era of drug discovery and development structural information play an important role. For visualization of 3D-structure of molecule different docking program are developed. The docking score is analysed by using computer-based drug design software. It is structure based virtual screening method for the orientation, conformation, position into a structure of target molecule. Ligand and Protein docking is new concept. Molecular docking method complication is optimization of lead molecule, biological pathway evaluation and de Novo drug design.

Discovering high-affinity ligands from the computationally predicted structures and affinities of small molecules bound to a target: A virtual screening approach

2000

We describe a 'virtual NMR screening' method to assist in the design of inhibitors that occupy different sites within a target. We dock small molecules into the active site of an enzyme and score them. Keeping the tightest-binding lead fixed in space, we dock and score other small molecules in its presence. Using this approach, linker groups are used to join the compounds together to form a high-affinity inhibitor. We present validation of our computational approach by reproducing experimental results for FKBP and stromelysin. Docking simulations are not subject to experimental problems such as proteolysis, protein or compound insolubility, or enzyme size. Because docking is fast and our scoring method can distinguish between high-and low-affinity inhibitors, this docking procedure shows promise as integral part of a drug-design strategy.

Computational Docking Technique for Drug Discovery: A Review

Research Journal of Pharmacy and Technology

Computational and experimental techniques are two complimentary approaches that have important roles in drug discovery and development. Earlier time and cost of bringing a new drug in market bears a question as it takes seven to twelve years and $ 1.2 billion are often cited. Furthermore, five out of forty thousand compounds tested in animals reach human testing and only one of five compounds reaching clinical studies is approved. This accounts for a large input in terms of time, money and human and other resources. Therefore, new approaches are needed to facilitate, expedite and streamline drug discovery and development, save time, money and resources. Among many computational tools, molecular docking is one of the important means that can be used in drug discovery. It provides the information regarding the binding affinities between small molecules (ligands) and macromolecular receptor targets (proteins). Various approaches, methodology are cited in various literatures for describ...