Using the generalized Born surface area model to fold proteins yields more effective sampling while qualitatively preserving the folding landscape

Peng Tao and Yi Xiao

Phys. Rev. E 101, 062417 – Published 22 June 2020

Abstract

Protein folding is a long-standing problem and has been widely investigated using molecular dynamics simulations with both explicit and implicit solvents. However, to what extent the folding mechanisms observed in two water models agree remains an open question. In this study, ab initio folding simulations of ten proteins with different topologies are performed in two combinations of force fields and water models (ff14SB+TIP3P and ff14SBonlysc+GB-Neck2). Interestingly, the latter combination not only folds more proteins but also provides a better balance of different secondary structures than the former in the same number of integration time steps. More importantly, the folding pathways found in the two types of simulations are conserved and they may only differ in their weights. Our results suggest that simulations with an implicit solvent may also be suitable for the investigation of the mechanism of protein folding.