Protein Folding in Denaturants By the Karanicolas-Brooks (KB) Go-like Model

Protein folding/unfolding in denaturants such as urea and guanidinium chloride has been thoroughly studied experimentally. On the simulation side, the molecular transfer model (MTM) is recently developed by O’Brien et. al to predict protein folding equilibrium in denaturants and osmolytes by performing the simulation with a two-beads coarse grained protein model and reweighting the ensemble with respect to each solvent condition based on the Tanford's transfer model. In this work, by using the similar idea and rescaling the parameters obtained from the MTM, we implement a simulation method of protein folding in denaturants using the KB Go-like model. Instead of reconstructing the all-atom structure as the MTM, we employ an optimized fast solvent accessible surface area estimator (POPS by Cavallo et. al) to directly calculate the residue-based SASA based on the Cα information only. Therefore, the free energy contribution of the solvent is able to be measured and included in the simulation sampling on the fly. The preliminary results shows great consistency in the predicted change of protein melting temperature from simulations and the experimentally measured values. Different thermally stable intermediates of protein folding in denaturants can also be captured by this simulation method, which may not be available by experimental measurements.