Toward Optimized Potential Functions for Protein鈥揚rotein Interactions in Aqueous Solutions: Osmotic Second Virial Coefficient Calculations Using the MARTINI Coarse-Grained Force Field

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• 作者：Austin C. Stark ; Casey T. Andrews ; Adrian H. Elcock
• 刊名：Journal of Chemical Theory and Computation
• 出版年：2013
• 出版时间：September 10, 2013
• 年：2013
• 卷：9
• 期：9
• 页码：4176-4185
• 全文大小：353K
• 年卷期：v.9,no.9(September 10, 2013)
• ISSN：1549-9626

文摘

Coarse-grained (CG) simulation methods are now widely used to model the structure and dynamics of large biomolecular systems. One important issue for using such methods鈥攅specially with regard to using them to model, for example, intracellular environments鈥攊s to demonstrate that they can reproduce experimental data on the thermodynamics of protein鈥損rotein interactions in aqueous solutions. To examine this issue, we describe here simulations performed using the popular coarse-grained MARTINI force field, aimed at computing the thermodynamics of lysozyme and chymotrypsinogen self-interactions in aqueous solution. Using molecular dynamics simulations to compute potentials of mean force between a pair of protein molecules, we show that the original parametrization of the MARTINI force field is likely to significantly overestimate the strength of protein鈥損rotein interactions to the extent that the computed osmotic second virial coefficients are orders of magnitude more negative than experimental estimates. We then show that a simple down-scaling of the van der Waals parameters that describe the interactions between protein pseudoatoms can bring the simulated thermodynamics into much closer agreement with experiment. Overall, the work shows that it is feasible to test explicit-solvent CG force fields directly against thermodynamic data for proteins in aqueous solutions and highlights the potential usefulness of osmotic second virial coefficient measurements for fully parametrizing such force fields.