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J Chem Theory Comput. 2019 Jun 11;15(6):3844-3853. doi: 10.1021/acs.jctc.8b01254. Epub 2019 May 14.

Configurational Entropy Components and Their Contribution to Biomolecular Complex Formation.

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University of Vienna , Max F. Perutz Laboratories, Department of Structural and Computational Biology , Campus Vienna Biocenter 5 , Vienna 1030 , Austria.
University of Vienna , Faculty of Chemistry, Department of Computational Biological Chemistry , Währinger Straße 17 , Vienna 1090 , Austria.


Configurational entropy change is a central constituent of the free energy change in noncovalent interactions between biomolecules. Due to both experimental and computational limitations, however, the impact of individual contributions to configurational entropy change remains underexplored. Here, we develop a novel, fully analytical framework to dissect the configurational entropy change of binding into contributions coming from molecular internal and external degrees of freedom. Importantly, this framework accounts for all coupled and uncoupled contributions in the absence of an external field. We employ our parallel implementation of the maximum information spanning tree algorithm to provide a comprehensive numerical analysis of the importance of the individual contributions to configurational entropy change on an extensive set of molecular dynamics simulations of protein binding processes. Contrary to commonly accepted assumptions, we show that different coupling terms contribute significantly to the overall configurational entropy change. Finally, while the magnitude of individual terms may be largely unpredictable a priori, the total configurational entropy change can be well approximated by rescaling the sum of uncoupled contributions from internal degrees of freedom only, providing support for NMR-based approaches for configurational entropy change estimation.

[Indexed for MEDLINE]

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