Abstract
With the number of protein-ligand complexes available in the Protein Data Bank constantly growing, structure-based approaches to drug design and screening have become increasingly important. Alongside this explosion of structural information, a number of molecular docking methods have been developed over the last years with the aim of maximally exploiting all available structural and chemical information that can be derived from proteins, from ligands, and from protein-ligand complexes. In this respect, the term guided docking is introduced to refer to docking approaches that incorporate some degree of chemical information to actively guide the orientation of the ligand into the binding site. To reflect the focus on the use of chemical information, a classification scheme for guided docking approaches is proposed. In general terms, guided docking approaches can be divided into indirect and direct approaches. Indirect approaches incorporate chemical information implicitly, having an effect on scoring but not on orienting the ligand during sampling. In contrast, direct approaches incorporate chemical information explicitly, thus actively guiding the orientation of the ligand during sampling. Direct approaches can be further divided into protein-based, mapping-based, and ligandbased approaches to reflect the source used to derive the features capturing the chemical information inside the protein cavity. Within each category, a representative list of docking approaches is discussed. In view of the limitations of current scoring functions, it was generally found that making optimal use of chemical information represents an efficient knowledge-based strategy for improving binding affinity estimations, ligand binding-mode predictions, and virtual screening enrichments obtained from protein-ligand docking.
Keywords: protein, protein-ligand
Current Topics in Medicinal Chemistry
Title: Guided Docking Approaches to Structure-Based Design and Screening
Volume: 4 Issue: 7
Author(s): Xavier Fradera and Jordi Mestres
Affiliation:
Keywords: protein, protein-ligand
Abstract: With the number of protein-ligand complexes available in the Protein Data Bank constantly growing, structure-based approaches to drug design and screening have become increasingly important. Alongside this explosion of structural information, a number of molecular docking methods have been developed over the last years with the aim of maximally exploiting all available structural and chemical information that can be derived from proteins, from ligands, and from protein-ligand complexes. In this respect, the term guided docking is introduced to refer to docking approaches that incorporate some degree of chemical information to actively guide the orientation of the ligand into the binding site. To reflect the focus on the use of chemical information, a classification scheme for guided docking approaches is proposed. In general terms, guided docking approaches can be divided into indirect and direct approaches. Indirect approaches incorporate chemical information implicitly, having an effect on scoring but not on orienting the ligand during sampling. In contrast, direct approaches incorporate chemical information explicitly, thus actively guiding the orientation of the ligand during sampling. Direct approaches can be further divided into protein-based, mapping-based, and ligandbased approaches to reflect the source used to derive the features capturing the chemical information inside the protein cavity. Within each category, a representative list of docking approaches is discussed. In view of the limitations of current scoring functions, it was generally found that making optimal use of chemical information represents an efficient knowledge-based strategy for improving binding affinity estimations, ligand binding-mode predictions, and virtual screening enrichments obtained from protein-ligand docking.
Export Options
About this article
Cite this article as:
Fradera Xavier and Mestres Jordi, Guided Docking Approaches to Structure-Based Design and Screening, Current Topics in Medicinal Chemistry 2004; 4 (7) . https://dx.doi.org/10.2174/1568026043451104
DOI https://dx.doi.org/10.2174/1568026043451104 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
Chemistry Based on Natural Products for Therapeutic Purposes
The development of new pharmaceuticals for a wide range of medical conditions has long relied on the identification of promising natural products (NPs). There are over sixty percent of cancer, infectious illness, and CNS disease medications that include an NP pharmacophore, according to the Food and Drug Administration. Since NP ...read more
Current Trends in Drug Discovery Based on Artificial Intelligence and Computer-Aided Drug Design
Drug development discovery has faced several challenges over the years. In fact, the evolution of classical approaches to modern methods using computational methods, or Computer-Aided Drug Design (CADD), has shown promising and essential results in any drug discovery campaign. Among these methods, molecular docking is one of the most notable ...read more
Drug Discovery in the Age of Artificial Intelligence
In the age of artificial intelligence (AI), we have witnessed a significant boom in AI techniques for drug discovery. AI techniques are increasingly integrated and accelerating the drug discovery process. These developments have not only attracted the attention of academia and industry but also raised important questions regarding the selection ...read more
From Biodiversity to Chemical Diversity: Focus of Flavonoids
Flavonoids are the largest group of polyphenols, plant secondary metabolites arising from the essential aromatic amino acid phenylalanine (or more rarely from tyrosine) via the phenylpropanoid pathway. The flavan nucleus is the basic 15-carbon skeleton of flavonoids (C6-C3-C6), which consists of two phenyl rings (A and B) and a heterocyclic ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
<sup>18</sup>F-Labeled Aryl-Tracers through Direct Introduction of [<sup>18</sup>F]fluoride into Electron-Rich Arenes
Current Organic Chemistry Glycosides from Medicinal Plants as Potential Anticancer Agents: Emerging Trends Towards Future Drugs
Current Medicinal Chemistry Synthesis and Biological Evaluation of Pyrazolo[3,4-<i>b</i>]pyridin-4-ones as a New Class of Topoisomerase II Inhibitors
Medicinal Chemistry Non Peptidic Ligands at the Opioid Receptor Like-1 (ORL-1)
Mini-Reviews in Medicinal Chemistry Tocilizumab: From Rheumatic Diseases to COVID-19
Current Pharmaceutical Design Experimental Antiarrhythmic Targets: CaMKII Inhibition – Ready for Clinical Evaluation?
Current Medicinal Chemistry Therapeutic Potential for Thyroid Hormone Receptor-β Selective Agonists for Treating Obesity, Hyperlipidemia and Diabetes
Current Vascular Pharmacology The Present Utility and Future Potential for Medicinal Chemistry of QSAR / QSPR with Whole Molecule Descriptors
Current Topics in Medicinal Chemistry Potential Application of Gene Therapy to X-Linked Agammaglobulinemia
Current Gene Therapy Coronavirus Disease 2019 (COVID-19) and Pregnancy: A Narrative Review
Current Pediatric Reviews Pesticides as Estrogen Disruptors: QSAR for Selective ERα and ERβ Binding of Pesticides
Combinatorial Chemistry & High Throughput Screening Omalizumab for Asthma: Indications, Off-Label Uses and Future Directions
Recent Patents on Inflammation & Allergy Drug Discovery Antimitotic Chalcones and Related Compounds as Inhibitors of Tubulin Assembly
Anti-Cancer Agents in Medicinal Chemistry NMN/NaMN Adenylyltransferase (NMNAT) and NAD Kinase (NADK) Inhibitors: Chemistry and Potential Therapeutic Applications
Current Medicinal Chemistry Recent Advances in the Discovery of Selective and Non-Selective 5-HT1D Receptor Ligands
Current Topics in Medicinal Chemistry Therapeutic Efficacy of Polyherbal Formulation Kabasura kudineer Against Common Viral Fevers - A Perspective Review
Anti-Infective Agents Targeting Cancer Using Fragment Based Drug Discovery
Anti-Cancer Agents in Medicinal Chemistry In Silico Prediction of P-glycoprotein Binding: Insights from Molecular Docking Studies
Current Medicinal Chemistry Impact on Pharmaceutical Industry due to Sudden Pandemic Attack (COVID-19)
Coronaviruses Microwave-Assisted Synthesis of Some New Benzimidazole Derivatives with their Antimicrobial Activity
Current Microwave Chemistry