Document Detail


Protein-ligand binding free energy calculation by the Smooth Reaction Path Generation (SRPG) Method.
MedLine Citation:
PMID:  19807195     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We developed a new molecular dynamics simulation method for protein-ligand binding free energy calculation in an explicit water model. This method consists of three steps: (1) generation of a compound dissociation path starting from a stable protein-compound complex structure, (2) calculation of the free energy surface along the dissociation path, and (3) calculation of the free energy surface of a small area around the protein-compound complex structure, which is a free energy minimum. The protein-compound binding free energy is estimated from the information obtained by the above three steps. This method was applied to a small system, a 18-crown-6 ether with its ligand ion, and a realistic system consisting of a target protein with its inhibitor. This approximation worked well; the protein-inhibitor dissociation was successfully performed, and the binding free energies were calculated.
Authors:
Yoshifumi Fukunishi; Daisuke Mitomo; Haruki Nakamura
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of chemical information and modeling     Volume:  49     ISSN:  1549-9596     ISO Abbreviation:  -     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-10-07     Completed Date:  2009-10-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101230060     Medline TA:  J Chem Inf Model     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1944-51     Citation Subset:  IM    
Affiliation:
Biomedicinal Information Research Center (BIRC), National Institute of Advanced Industrial Science and Technology (AIST), Tokyo, Japan. y-fukunishi@aist.go.jp
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MeSH Terms
Descriptor/Qualifier:
Biotin / chemistry,  metabolism
Computer Simulation
Crown Ethers / chemistry
Ligands
Models, Molecular
Molecular Conformation
Protein Binding
Proteins / antagonists & inhibitors,  chemistry*,  metabolism
Streptavidin / antagonists & inhibitors,  chemistry,  metabolism
Thermodynamics*
Chemical
Reg. No./Substance:
0/Crown Ethers; 0/Ligands; 0/Proteins; 58-85-5/Biotin; 9013-20-1/Streptavidin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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