Abstract
The potential energy hyper-surface of a protein relates the potential energy of the protein to its conformational space. This surface is useful in determining the native conformation of a protein or in examining a statistical-mechanical ensemble of structures (canonical ensemble). In determining the potential energy hyper-surface of a protein three aspects must be considered; reducing the degrees of freedom, a method to determine the energy of each conformation and a method to sample the conformational space. For reducing the degrees of freedom the choice of solvent, coarse graining, constraining degrees of freedom and periodic boundary conditions are discussed. The use of quantum mechanics versus molecular mechanics and the choice of force fields are also discussed, as well as the sampling of the conformational space through deterministic and heuristic approaches. Deterministic methods include knowledge-based statistical methods, rotamer libraries, homology modeling, the build-up method, self-consistent electrostatic field, deformation methods, tree-based elimination and eigenvector following routines. The heuristic methods include Monte Carlo chain growing, energy minimizations, metropolis monte carlo and molecular dynamics. In addition, various methods to enhance the conformational search including the deformation or smoothing of the surface, scaling of system parameters, and multi copy searching are also discussed.
Keywords: Protein, potential energy surface, native state, lowest energy state, conformational sampling, structure determination, molecular dynamics.
Current Pharmaceutical Design
Title:Conformational Sampling Techniques
Volume: 20 Issue: 20
Author(s): Marcus P. D. Hatfield and Sandor Lovas
Affiliation:
Keywords: Protein, potential energy surface, native state, lowest energy state, conformational sampling, structure determination, molecular dynamics.
Abstract: The potential energy hyper-surface of a protein relates the potential energy of the protein to its conformational space. This surface is useful in determining the native conformation of a protein or in examining a statistical-mechanical ensemble of structures (canonical ensemble). In determining the potential energy hyper-surface of a protein three aspects must be considered; reducing the degrees of freedom, a method to determine the energy of each conformation and a method to sample the conformational space. For reducing the degrees of freedom the choice of solvent, coarse graining, constraining degrees of freedom and periodic boundary conditions are discussed. The use of quantum mechanics versus molecular mechanics and the choice of force fields are also discussed, as well as the sampling of the conformational space through deterministic and heuristic approaches. Deterministic methods include knowledge-based statistical methods, rotamer libraries, homology modeling, the build-up method, self-consistent electrostatic field, deformation methods, tree-based elimination and eigenvector following routines. The heuristic methods include Monte Carlo chain growing, energy minimizations, metropolis monte carlo and molecular dynamics. In addition, various methods to enhance the conformational search including the deformation or smoothing of the surface, scaling of system parameters, and multi copy searching are also discussed.
Export Options
About this article
Cite this article as:
Hatfield P. D. Marcus and Lovas Sandor, Conformational Sampling Techniques, Current Pharmaceutical Design 2014; 20 (20) . https://dx.doi.org/10.2174/13816128113199990603
DOI https://dx.doi.org/10.2174/13816128113199990603 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
Call for Papers in Thematic Issues
"Tuberculosis Prevention, Diagnosis and Drug Discovery"
The Nobel Prize-winning discoveries of Mycobacterium tuberculosis and streptomycin have enabled an appropriate diagnosis and an effective treatment of tuberculosis (TB). Since then, many newer diagnosis methods and drugs have been saving millions of lives. Despite advances in the past, TB is still a leading cause of infectious disease mortality ...read more
Current Pharmaceutical challenges in the treatment and diagnosis of neurological dysfunctions
Neurological dysfunctions (MND, ALS, MS, PD, AD, HD, ALS, Autism, OCD etc..) present significant challenges in both diagnosis and treatment, often necessitating innovative approaches and therapeutic interventions. This thematic issue aims to explore the current pharmaceutical landscape surrounding neurological disorders, shedding light on the challenges faced by researchers, clinicians, and ...read more
Emerging and re-emerging diseases
Faced with a possible endemic situation of COVID-19, the world has experienced two important phenomena, the emergence of new infectious diseases and/or the resurgence of previously eradicated infectious diseases. Furthermore, the geographic distribution of such diseases has also undergone changes. This context, in turn, may have a strong relationship with ...read more
Melanoma and Non-Melanoma Skin Cancer Treatment: Standard of Care and Recent Advances
In this thematic issue, we aim to provide a standard of care of the diagnosis and treatment of melanoma and non-melanoma skin cancer. The editor will invite authors from different countries who will write review articles of melanoma and non-melanoma skin cancers. The Diagnosis, Staging, Surgical Treatment, Non-Surgical Treatment all ...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
-
Pharmacologic Treatment of Pulmonary Arterial Hypertension
Current Pharmaceutical Design Platelet-Monocyte Interactions - A Dangerous Liaison Linking Thrombosis, Inflammation and Atherosclerosis
Current Medicinal Chemistry Pulmonary Hypertension and Lung Transplantation
Current Hypertension Reviews Long-Term Outcome of Cardio Respiratory Exercise Performance After Surgery
Current Respiratory Medicine Reviews Chest Pain in Children
Current Pediatric Reviews Computer Simulations of Alzheimers Amyloid β-Protein Folding and Assembly
Current Alzheimer Research Surface Chemical Functional Groups Modification of Porous Carbon
Recent Patents on Chemical Engineering Castration Resistant Prostate Cancer (CRPC): State of the Art, Perspectives and New Challenges
Anti-Cancer Agents in Medicinal Chemistry Genetics and Personalized Medicine in Antidepressant Treatment
Current Pharmaceutical Design Antibody-Ligand Interactions: Computational Modeli ng and Correlation with Biophysical Measurements
Combinatorial Chemistry & High Throughput Screening A Review of Selected Adult Congenital Heart Diseases Encountered in Daily Practice
Current Cardiology Reviews Cardiovascular Diseases in Pregnancy - A Brief Overview
Current Cardiology Reviews Generalized-Ensemble Algorithms for Protein Folding and Unfolding
Current Physical Chemistry Microcirculatory Endothelial Dysfunction During Endotoxemia - Insights into Pathophysiology, Pathologic Mechanisms and Clinical Relevance
Current Vascular Pharmacology Radiation and Gene Therapy: Rays of Hope for the New Millennium?
Current Gene Therapy Augmentation Strategies to Improve Treatment of Major Depression
Central Nervous System Agents in Medicinal Chemistry The Adult Patient with Eisenmenger Syndrome: A Medical Update after Dana Point Part II: Medical Treatment - Study Results
Current Cardiology Reviews Pulmonary Arterial Hypertension in HIV-infected Patients
Current Hypertension Reviews The Role of a Human Hematopoietic Mesenchymal Progenitor in Wound Healing and Fibrotic Diseases and Implications for Therapy
Current Stem Cell Research & Therapy Pathophysiology of Platelet Resistance to Anti-Aggregating Agents in Insulin Resistance and Type 2 Diabetes: Implications for Anti-Aggregating Therapy
Cardiovascular & Hematological Agents in Medicinal Chemistry