Evaluation of the Coupled Two-Dimensional Main Chain Torsional Potential in Modeling Intrinsically Disordered Proteins

Intrinsically
disordered proteins (IDPs) carry out crucial biological
functions in essential biological processes of life. Because of the
highly dynamic and conformationally heterogeneous nature of the disordered
states of IDPs, molecular dynamics simulations are becoming an indispensable
tool for the investigation of the conformational ensembles and dynamic
properties of IDPs. Nevertheless, there is still no consensus on the
most reliable force field in molecular dynamics simulations for IDPs
hitherto. In this work, the recently proposed AMBER99SB2D force field is evaluated in modeling some disordered polypeptides
and proteins by checking its ability to reproduce experimental NMR
data. The results highlight that when the ildn side-chain corrections
are included, AMBER99SB2D-ildn exhibits reliable results
that agree with experiments compared with its predecessors, the AMBER14SB,
AMBER99SB, AMBER99SB-ildn, and AMBER99SB2D force fields,
and that decreasing the overall magnitude of protein–protein
interactions in favor of protein–water interactions is a key
ingredient behind the improvement.