Correlation as a Determinant of Configurational Entropy in Supramolecular and Protein Systems

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• 作者：Andrew T. Fenley ; Benjamin J. Killian ; Vladimir Hnizdo ; Adam Fedorowicz ; Dan S. Sharp ; Michael K. Gilson
• 刊名：Journal of Physical Chemistry B
• 出版年：2014
• 出版时间：June 19, 2014
• 年：2014
• 卷：118
• 期：24
• 页码：6447-6455
• 全文大小：361K
• 年卷期：v.118,no.24(June 19, 2014)
• ISSN：1520-5207

文摘

For biomolecules in solution, changes in configurational entropy are thought to contribute substantially to the free energies of processes like binding and conformational change. In principle, the configurational entropy can be strongly affected by pairwise and higher-order correlations among conformational degrees of freedom. However, the literature offers mixed perspectives regarding the contributions that changes in correlations make to changes in configurational entropy for such processes. Here we take advantage of powerful techniques for simulation and entropy analysis to carry out rigorous in silico studies of correlation in binding and conformational changes. In particular, we apply information-theoretic expansions of the configurational entropy to well-sampled molecular dynamics simulations of a model host鈥揼uest system and the protein bovine pancreatic trypsin inhibitor. The results bear on the interpretation of NMR data, as they indicate that changes in correlation are important determinants of entropy changes for biologically relevant processes and that changes in correlation may either balance or reinforce changes in first-order entropy. The results also highlight the importance of main-chain torsions as contributors to changes in protein configurational entropy. As simulation techniques grow in power, the mathematical techniques used here will offer new opportunities to answer challenging questions about complex molecular systems.