While the properties of folded proteins are generally well described in simulation, large discrepancies exist between simulation and experiment for more disordered states.  A number of force field modifications have been proposed to remedy these deficiencies, resulting in substantial improvements in the quality of simulations of disordered states.  One outstanding issue, however, is the extent to which these modifications are transferable to the simulation of more ordered systems.  To address this question, we assembled an extensive set of benchmark data to systematically assess the ability of commonly used molecular dynamics force fields to reproduce experimental NMR, SAXS, and FRET results for ordered and disordered biomolecules, and we found that none of the force fields investigated could accurately describe the properties of both ordered and disordered biomolecules.  Guided by experimental measurements from folded proteins, fast-folding proteins, weakly structured peptides, and disordered proteins, we have been able to further optimize force fields to more accurately simulate proteins across the order-to-disorder spectrum.

Challenges of developing biomolecular force fields for the accurate simulation of both ordered and disordered states

252nd National Meeting (2016)

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