Abstract
Although the motions of proteins are fundamental for their function, for pragmatic reasons, the consideration of protein elasticity has traditionally been neglected in drug discovery and design. This review details protein motion, its relevance to biomolecular interactions and how it can be sampled using molecular dynamics simulations. Within this context, two major areas of research in structure-based prediction that can benefit from considering protein flexibility, binding site detection and molecular docking, are discussed. Basic classification metrics and statistical analysis techniques, which can facilitate performance analysis, are also reviewed. With hardware and software advances, molecular dynamics in combination with traditional structure-based prediction methods can potentially reduce the time and costs involved in the hit identification pipeline.
Keywords: Computational methods, docking, drug design, flexibility, molecular dynamics, structure-based prediction, validation, statistical performance analysis.
Current Topics in Medicinal Chemistry
Title:Rational Prediction with Molecular Dynamics for Hit Identification
Volume: 12 Issue: 18
Author(s): Sara E. Nichols, Robert V. Swift and Rommie E. Amaro
Affiliation:
Keywords: Computational methods, docking, drug design, flexibility, molecular dynamics, structure-based prediction, validation, statistical performance analysis.
Abstract: Although the motions of proteins are fundamental for their function, for pragmatic reasons, the consideration of protein elasticity has traditionally been neglected in drug discovery and design. This review details protein motion, its relevance to biomolecular interactions and how it can be sampled using molecular dynamics simulations. Within this context, two major areas of research in structure-based prediction that can benefit from considering protein flexibility, binding site detection and molecular docking, are discussed. Basic classification metrics and statistical analysis techniques, which can facilitate performance analysis, are also reviewed. With hardware and software advances, molecular dynamics in combination with traditional structure-based prediction methods can potentially reduce the time and costs involved in the hit identification pipeline.
Export Options
About this article
Cite this article as:
E. Nichols Sara, V. Swift Robert and E. Amaro Rommie, Rational Prediction with Molecular Dynamics for Hit Identification, Current Topics in Medicinal Chemistry 2012; 12 (18) . https://dx.doi.org/10.2174/1568026611212180007
DOI https://dx.doi.org/10.2174/1568026611212180007 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |
Call for Papers in Thematic Issues
AlphaFold in Medicinal Chemistry: Opportunities and Challenges
AlphaFold, a groundbreaking AI tool for protein structure prediction, is revolutionizing drug discovery. Its near-atomic accuracy unlocks new avenues for designing targeted drugs and performing efficient virtual screening. However, AlphaFold's static predictions lack the dynamic nature of proteins, crucial for understanding drug action. This is especially true for multi-domain proteins, ...read more
Artificial intelligence for Natural Products Discovery and Development
Our approach involves using computational methods to predict the potential therapeutic benefits of natural products by considering factors such as drug structure, targets, and interactions. We also employ multitarget analysis to understand the role of drug targets in disease pathways. We advocate for the use of artificial intelligence in predicting ...read more
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
- 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
-
Targeting Antioxidants to Mitochondria: A Potential New Therapeutic Strategy for Cardiovascular Diseases
Current Pharmaceutical Design Neurological Soft Signs in Patients with Psychosis and Cannabis Abuse: A Systematic Review and Meta-Analysis of Paradox
Current Pharmaceutical Design Allergic Asthma: A Summary from Genetic Basis, Mouse Studies, to Diagnosis and Treatment
Current Pharmaceutical Design Adhesion Molecules as Targets for the Treatment of Neoplastic Diseases
Current Pharmaceutical Design Small Molecule CXCR4 Chemokine Receptor Antagonists: Developing Drug Candidates
Current Medicinal Chemistry Current Acetylcholinesterase-Inhibitors: A Neuroinformatics Perspective
CNS & Neurological Disorders - Drug Targets Renal and Urological Diseases of the Newborn Neonatal Acute Kidney Injury
Current Pediatric Reviews Voltage-Gated Ion Channels, New Targets in Anti-Cancer Research
Recent Patents on Anti-Cancer Drug Discovery Stem Cells Therapies in Basic Science and Translational Medicine: Current Status and Treatment Monitoring Strategies
Current Pharmaceutical Biotechnology CAM Use in Pediatric Oncology
Current Pediatric Reviews Defining a Role for Mucosal Immunity in the Prevention and Pathogenesis of Respiratory Allergic Diseases
Current Immunology Reviews (Discontinued) RNA Metabolism in Neurodegenerative Disease
Current Chemical Biology Insight to Physiology and Pathology of Zinc(II) Ions and Their Actions in Breast and Prostate Carcinoma
Current Medicinal Chemistry Meet Our Editorial Board Member
Current Alzheimer Research Alstrom Syndrome: Genetics and Clinical Overview
Current Genomics Ghrelin as a Neuroprotective and Palliative Agent in Alzheimer's and Parkinson's Disease
Current Pharmaceutical Design Herbal Insomnia Medications that Target GABAergic Systems: A Review of the Psychopharmacological Evidence
Current Neuropharmacology Leveraging NMR and X-ray Data of the Free Ligands to Build Better Drugs Targeting Angiotensin II Type 1 G-Protein Coupled Receptor
Current Medicinal Chemistry Elevated Homocysteine Levels in Parkinsons Disease: Is there Anything Besides L-Dopa Treatment?
Current Medicinal Chemistry Methodological Aspects of Erythrocyte Aggregation
Recent Patents on Anti-Cancer Drug Discovery