Enhanced ab initio protein folding simulations in Poisson-Boltzmann molecular dynamics with self-guiding forces

We have investigated the sampling efficiency in molecular dynamics with the PB implicit solvent when self-guiding forces are added. Compared with a high-temperature dynamics simulation, the use of self-guiding forces in room-temperature dynamics is found to be rather efficient as measured by potential energy fluctuation, gyration radius fluctuation, backbone RMSD fluctuation, number of unique clusters, and distribution of low RMSD structures over simulation time. Based on the enhanced sampling method, we have performed ab initio folding simulations of two small proteins, betabetaalpha1 and villin headpiece. The preliminary data for the folding simulations is presented. It is found that betabetaalpha1 folding proceeds by initiation of the turn and the helix. The hydrophobic collapse seems to be lagging behind or at most concurrent with the formation of the helix. The hairpin stability is weaker than the helix in our simulations. Its role in the early folding events seems to be less important than the more stable helix. In contrast, villin headpiece folding proceeds first by hydrophobic collapse. The formation of helices is later than the collapse phase, different from the betabetaalpha1 folding.