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CHARMM-GUI Ligand Binder for Absolute Binding Free Energy Calculations and Its Application
dc.contributor.author | Jo, Sunhwan | |
dc.contributor.author | Jiang, Wei | |
dc.contributor.author | Lee, Hui Sun | |
dc.contributor.author | Roux, Benoît | |
dc.contributor.author | Im, Wonpil | |
dc.date.accessioned | 2017-05-16T18:18:23Z | |
dc.date.available | 2017-05-16T18:18:23Z | |
dc.date.issued | 2013-01-28 | |
dc.identifier.citation | Jo, S., Jiang, W., Lee, H. S., Roux, B., & Im, W. (2013). CHARMM-GUI Ligand Binder for Absolute Binding Free Energy Calculations and Its Application. Journal of Chemical Information and Modeling, 53(1), 267–277. http://doi.org/10.1021/ci300505n | en_US |
dc.identifier.uri | http://hdl.handle.net/1808/24226 | |
dc.description.abstract | 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 (http://www.charmm-gui.org/input/gbinding), 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 setup 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 non-polar 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). CHARMM-GUI Ligand Binder provides a convenient and reliable way to setup the ligand binding free energy calculations and can be applicable to pharmaceutically important protein-ligand systems. | en_US |
dc.publisher | American Chemical Society | en_US |
dc.rights | This document is the Accepted Manuscript version of a Published Work that appeared in final form in Journal of Chemical Information and Modeling, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://doi.org/10.1021/ci300505n. | en_US |
dc.subject | Free energy perturbation | en_US |
dc.subject | Molecular dynamics | en_US |
dc.subject | Protein-ligand Interactions | en_US |
dc.subject | T4 Lysozyme | en_US |
dc.subject | FKBP12 | en_US |
dc.title | CHARMM-GUI Ligand Binder for Absolute Binding Free Energy Calculations and Its Application | en_US |
dc.type | Article | en_US |
kusw.kuauthor | Jo, Sunhwan | |
kusw.kuauthor | Lee, Hui Sun | |
kusw.kuauthor | Im, Wonpil | |
kusw.kudepartment | Molecular Biosciences | en_US |
dc.identifier.doi | 10.1021/ci300505n | en_US |
dc.identifier.orcid | https://orcid.org/0000-0002-4104-6473 | |
kusw.oaversion | Scholarly/refereed, author accepted manuscript | en_US |
kusw.oapolicy | This item meets KU Open Access policy criteria. | en_US |
dc.identifier.pmid | PMC3557591 | en_US |
dc.rights.accessrights | openAccess |