Document Detail

CHARMM-GUI Ligand Binder for absolute binding free energy calculations and its application.
MedLine Citation:
PMID:  23205773     Owner:  NLM     Status:  MEDLINE    
Advanced free energy perturbation molecular dynamics (FEP/MD) simulation methods are available to accurately calculate absolute binding free energies of protein-ligand complexes. However, these methods rely on several sophisticated command scripts implementing various biasing energy restraints to enhance the convergence of the FEP/MD calculations, which must all be handled properly to yield correct results. Here, we present a user-friendly Web interface, CHARMM-GUI Ligand Binder ( ), to provide standardized CHARMM input files for calculations of absolute binding free energies using the FEP/MD simulations. A number of features are implemented to conveniently set up the FEP/MD simulations in highly customizable manners, thereby permitting an accelerated throughput of this important class of computations while decreasing the possibility of human errors. The interface and a series of input files generated by the interface are tested with illustrative calculations of absolute binding free energies of three nonpolar aromatic ligands to the L99A mutant of T4 lysozyme and three FK506-related ligands to FKBP12. Statistical errors within individual calculations are found to be small (~1 kcal/mol), and the calculated binding free energies generally agree well with the experimental measurements and the previous computational studies (within ~2 kcal/mol). Therefore, CHARMM-GUI Ligand Binder provides a convenient and reliable way to set up the ligand binding free energy calculations and can be applicable to pharmaceutically important protein-ligand systems.
Sunhwan Jo; Wei Jiang; Hui Sun Lee; Benoît Roux; Wonpil Im
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2012-12-20
Journal Detail:
Title:  Journal of chemical information and modeling     Volume:  53     ISSN:  1549-960X     ISO Abbreviation:  J Chem Inf Model     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2013-01-28     Completed Date:  2013-07-22     Revised Date:  2014-01-29    
Medline Journal Info:
Nlm Unique ID:  101230060     Medline TA:  J Chem Inf Model     Country:  United States    
Other Details:
Languages:  eng     Pagination:  267-77     Citation Subset:  IM    
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MeSH Terms
Computer Graphics
Molecular Dynamics Simulation*
Protein Conformation
Proteins / chemistry*,  metabolism*
Solvents / chemistry
User-Computer Interface
Grant Support
Reg. No./Substance:
0/Ligands; 0/Proteins; 0/Solvents

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