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 namediDrude2019IDP/ibased oniDrude2019/iwith reweighting and grid-based potential energy correction map optimization. In order to evaluate the performance ofiDrude2019IDP/i, 16 dipeptides, 18 short peptides, 3 representative IDPs, and 5 structural proteins were simulated. The results show that the NMR observables driven byiDrude2019IDP/iare in better agreement with the experiment data than those byiDrude2019/ion short peptides and IDPs.iDrude2019IDP/ican sample more diverse conformations thaniDrude2019/i. Furthermore, the performances of the two force fields are similar to the sample ordered proteins. These results confirm that the developediDrude2019IDP/ican improve the reproduction of conformers for intrinsically disordered proteins and can be used to gain insight into the paradigm of sequence-disorder for IDPs.