Empirical force fields constitute the underlying models for major computational tools to study polypeptide and protein structure-dynamics-activity relationship. Explicit inclusion of electronic polarizability into force fields represents an important step for further improving the accuracy of protein force fields, and thus could lead to better understanding of protein conformational dynamics. Here we will give an overview on the development of the polarizable protein force field based on the classical Drude oscillator model, and illustrate its advantage in the conformational sampling of polypeptides and proteins. Results will include the importance of explicit induction in modeling the cooperativity of protein folding and aggregation illustrated based on gas phase quantum chemistry calculations and explicit solvent replica exchange simulations. We will also show how the Drude protein force field is capable of generating conformational sampling of proteins that are consistent with NMR and SAXS measurements, with discrepancies between simulation results and experimental data being highlighted. In addition, we will present our efforts towards future improvements in the Drude protein force field.

Conformational sampling of proteins with the fully polarizable Drude force field

254th National Meeting (2017)

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