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J Chem Theory Comput. 2017 Nov 14;13(11):5173-5178. doi: 10.1021/acs.jctc.7b00791. Epub 2017 Oct 9.

New Coarse Variables for the Accurate Determination of Standard Binding Free Energies.

Fu H1, Cai W1,2, Hénin J3, Roux B4,5, Chipot C6,7,8.

Author information

1
Research Center for Analytical Sciences, College of Chemistry, Tianjin Key Laboratory of Biosensing and Molecular Recognition, Nankai University , Tianjin 300071, China.
2
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin) , Tianjin 300071, China.
3
Laboratoire de Biochimie Théorique, CNRS and Institut de Biologie Physico-Chimique , 13, rue Pierre et Marie Curie, 75005 Paris, France.
4
Department of Biochemistry and Molecular Biology, Gordon Center for Integrative Science, University of Chicago , Chicago, Illinois 60637, United States.
5
Leadership Computing Facility, Argonne National Laboratory , 9700 Cass Avenue, Building 240, Argonne, Illinois 60439, United States.
6
Laboratoire International Associé Centre National de la Recherche Scientifique et University of Illinois at Urbana-Champaign, Unité Mixte de Recherche No. 7565, Université de Lorraine , B.P. 70239, 54506 Cedex Vandœuvre-lès-Nancy, France.
7
Theoretical and Computational Biophysics Group, Beckman Institute, University of Illinois at Urbana-Champaign , Urbana, Illinois 61801, United States.
8
Department of Physics, University of Illinois at Urbana-Champaign , 1110 West Green Street, Urbana, Illinois 61801, United States.

Abstract

To improve sampling of the configurational entropy change upon protein-ligand binding, we have introduced a new set of coarse variables describing the relative orientation and position of the ligand via a global macromolecular orientational procedure, onto which geometrical restraints are applied. Evaluating the potential of mean force for the different coarse variables, the experimental standard binding free energy for three decapeptides associated with the SH3 domain of the Abl kinase is reproduced quantitatively.

PMID:
28965398
DOI:
10.1021/acs.jctc.7b00791

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