Protein-ligand interaction energy-based entropy calculations: fundamental challenges for flexible systems

Gergely Kohut , Józef Adam Liwo , Szilvia Bösze , Tamás Beke-Somfai , Sergey Samsonov

Abstract

Entropy calculations represent one of the most challenging steps in obtaining the binding free energy in biomolecular systems. A novel computationally effective approach (IE) was recently proposed to calculate the entropy based on the computation of protein-ligand interaction energy directly from molecular dynamics (MD) simulations. We present a study focused on the application of this method to flexible molecular systems and compare its performance with well-established normal mode (NM) and quasiharmonic (QH) entropy calculation approaches. Our results demonstrated that the IE method is intended for calculating entropy change for binding partners in fixed conformations, as by the original definition of IE, and is not applicable to the molecular complexes in which the interacting partners undergo significant conformational changes during the binding process.
Author Gergely Kohut
Gergely Kohut,,
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, Józef Adam Liwo (FCh / DTCh / LMM)
Józef Adam Liwo,,
- Laboratory of Molecular Modeling
, Szilvia Bösze
Szilvia Bösze,,
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, Tamás Beke-Somfai
Tamás Beke-Somfai,,
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, Sergey Samsonov (FCh / DTCh / LMM)
Sergey Samsonov,,
- Laboratory of Molecular Modeling
Journal seriesJournal of Physical Chemistry B, ISSN 1520-6106, (A 30 pkt)
Issue year2018
Vol122
No32
Pages7821-7827
Publication size in sheets0.5
DOIDOI:10.1021/acs.jpcb.8b03658
URL https://pubs.acs.org/doi/pdf/10.1021/acs.jpcb.8b03658
Languageen angielski
Score (nominal)30
ScoreMinisterial score = 30.0, 31-08-2018, ArticleFromJournal
Ministerial score (2013-2016) = 30.0, 31-08-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2016 = 3.177 (2) - 2016=3.177 (5)
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