Molecular dynamics simulations of folded proteins: determining the properties of protein cores

Proteins are highly dynamic molecules that undergo conformational fluctuations on temporal and spatial scales. Theseconformational changes, often intimately connected to the functional forms of the proteins. Molecular dynamics (MD)simulations have provided ways to estimate the hidden conformations and understand the correlation between confor-mation change and their functions. However, whether MD can accurately recapitulate protein dynamics still remainsunclear. In this paper, we show that three of the most commonly used MD force fields, CHARMM36M, Amber99SB-ILDN and Amber99NMR cannot accurately recapitulate the conformations of proteins solved by solution NMR. Eventhough the MD simulations are initiated with the experimental structures, they quickly diverge from the NMR bundle.