50 Years of Lifson鈥揜oig Models: Application to Molecular Simulation Data

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• 作者：Andreas Vitalis ; Amedeo Caflisch
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2012
• 出版时间：January 10, 2012
• 年：2012
• 卷：8
• 期：1
• 页码：363-373
• 全文大小：635K
• 年卷期：v.8,no.1(January 10, 2012)
• ISSN：1549-9626

文摘

Simple helix鈥揷oil transition theories have been indispensable tools in the analysis of data reporting on the reversible folding of 伪-helical polypeptides. They provide a transferable means to not only characterize different systems but to also compare different techniques, viz., experimental probes monitoring helix鈥揷oil transitions in vitro or biomolecular force fields in silico. This article addresses several issues with the application of Lifson鈥揜oig theory to helix鈥揷oil transition data. We use computer simulation to generate two sets of ensembles for the temperature-controlled, reversible folding of the 21-residue, alanine-rich FS peptide. Ensembles differ in the rigidity of backbone bond angles and are analyzed using two distinct descriptors of helicity. The analysis unmasks an underlying phase diagram that is surprisingly complex. The complexities give rise to fitted nucleation and propagation parameters that are difficult to interpret and that are inconsistent with the distribution of isolated residues in the 伪-helical basin. We show that enthalpies of helix formation are more robustly determined using van鈥檛 Hoff analysis of simple measures of helicity rather than fitted propagation parameters. To overcome some of these issues, we design a simple variant of the Lifson鈥揜oig model that recovers physical interpretability of the obtained parameters by allowing bundle formation to be described in simple fashion. The relevance of our results is discussed in relation to the applicability of Lifson鈥揜oig models to both in silico and in vitro data.