Successful ab initio folding of proteins with both α -helix and Β -sheet requires a delicate balance among a variety of forces in the simulation model, which may explain that the successful folding of any α/Β proteins to within experimental error has yet to be reported. Here we demonstrate that it is an achievable goal to fold α/Β proteins with a force field emphasizing the balance between the two major secondary structures. Using our newly developed force field, we conducted extensive ab initio folding simulations on an α/Β protein full sequence design (FSD) employing both conventional molecular dynamics and replica exchange molecular dynamics in combination with a generalized-Born solvation model. In these simulations, the folding of FSD to the native state with high population (*gt;64.2%) and high fidelity (Cα -Root Mean Square Deviation of 1.29 Å for the most sampled conformation when compared to the experimental structure) was achieved. The folding of FSD was found to follow two pathways. In the major pathway, the folding started from the formation of the helix. In the minor pathway, however, folding of the Β -hairpin started first. Further examination revealed that the helix initiated from the C-terminus and propagated toward the N-terminus. The formation of the hydrophobic contacts coincided with the global folding. Therefore the hydrophobic force does not appear to be the driving force of the folding of this protein.
All Science Journal Classification (ASJC) codes
- Physics and Astronomy(all)
- Physical and Theoretical Chemistry