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
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
-
Ceruloplasmin, the Unique Multi-Copper Oxidase of Vertebrates
Protein & Peptide Letters Pregnancy, Programming and Preeclampsia: Gap Junctions at the Nexus of Pregnancy-induced Adaptation of Endothelial Function and Endothelial Adaptive Failure in PE
Current Vascular Pharmacology Pharmacological Management of Huntingtons Disease: An Evidence- Based Review
Current Pharmaceutical Design Nanofiber Scaffolds for Treatment of Spinal Cord Injury
Current Medicinal Chemistry Molecular Switch of AhR in Repression or Activation of Stem Cell Signaling
Current Signal Transduction Therapy Insights into Cellular Uptake of Nanoparticles
Current Drug Delivery Emerging RNA-based Drugs: siRNAs, microRNAs and Derivates
Central Nervous System Agents in Medicinal Chemistry Targeting Brain Cancer Cells by Nanorobot, a Promising Nanovehicle: New Challenges and Future Perspectives
CNS & Neurological Disorders - Drug Targets Advances in Dopamine D1 Receptor Ligands for Neurotherapeutics
Current Topics in Medicinal Chemistry Pediatric Catatonia: Updating An Old Syndrome in Young People
Current Psychiatry Reviews TRPC Channels and their Implications for Neurological Diseases
CNS & Neurological Disorders - Drug Targets The Contribution of Proteinase-Activated Receptors to Intracellular Signaling, Transcellular Transport and Autophagy in Alzheimer´s Disease
Current Alzheimer Research Cannabidiol Partially Blocks the Excessive Sleepiness in Hypocretindeficient Rats: Preliminary Data
CNS & Neurological Disorders - Drug Targets The Ayurvedic Bhasma: The Ancient Science of Nanomedicine
Recent Patents on Nanomedicine Molecular Biology of the Enzymes that Degrade Endocannabinoids
Current Drug Targets - CNS & Neurological Disorders Thioridazine: The Good and the Bad
Recent Patents on Anti-Infective Drug Discovery Interaction of NO and VIP in Gastrointestinal Smooth Muscle Relaxation
Current Pharmaceutical Design Does Calprotectin Represent a Regulatory Factor in Host Defense or a Drug Target in Inflammatory Disease?
Endocrine, Metabolic & Immune Disorders - Drug Targets Muscle Atrophy Classification: The Need for a Pathway-Driven Approach
Current Pharmaceutical Design Acute Methamphetamine and Benzylpiperazine Decrease Aggression- Related Behavior in Late Adolescent Male Rats
Current Psychopharmacology