Polarizable Force Field of Intrinsically Disordered Proteins with CMAP and Reweighting Optimization.

Intrinsically disordered proteins (IDPs) are highly structurally heterogeneous without a specific tertiary structure under physiology conditions and play key roles in the development of human diseases. Due to the characteristics of diverse conformations, as one of the important methods, molecular dynamics simulation can complement information for experimental methods. Because of the enrichment for charged amino acids for IDPs, polarizable force fields should be a good choice for the simulation of IDPs. However, current polarizable force fields are limited in sampling conformer features of IDPs. Therefore, a polarizable force field was released and named <i>Drude2019IDP</i> based on <i>Drude2019</i> with reweighting and grid-based potential energy correction map optimization. In order to evaluate the performance of <i>Drude2019IDP</i>, 16 dipeptides, 18 short peptides, 3 representative IDPs, and 5 structural proteins were simulated. The results show that the NMR observables driven by <i>Drude2019IDP</i> are in better agreement with the experiment data than those by <i>Drude2019</i> on short peptides and IDPs. <i>Drude2019IDP</i> can sample more diverse conformations than <i>Drude2019</i>. Furthermore, the performances of the two force fields are similar to the sample ordered proteins. These results confirm that the developed <i>Drude2019IDP</i> can improve the reproduction of conformers for intrinsically disordered proteins and can be used to gain insight into the paradigm of sequence-disorder for IDPs.