The ensemble folding dynamics of EF-hand domain in parvalbumin from a Monte Carlo simulation

The helix-loop-helix (i.e., EF-hand) is the most common motif in the superfamily of Ca2+-binding proteins. Parvalbumins, as the classical EF-hand proteins, are associated with the muscle relaxation/contration, the calcium buffering etc. The previous researches focus more of interest on the ion coupled/decoupled mechanism using molecular dynamics (MD) computations. We developed the novel approach instead of MD, in which the Landau free energy was introduced to describe the protein in term of the skeletal C-alpha chain. The unfolding and folding processes were simulated by the Glauber algorithm under the repeated heating and cooling cycles. The high-quality crystal structure (2PVB) was as the trigger of non-equilibrium dynamics simulation for parvalbumin-beta (Parv). The evolution of three dimensional structure during the folding was displayed for the residues 8-64 fragment in Parv. The phenomenon of helix nucleation was observed, that was, the 310 helix at residues 35-37 and the front of alpha-helix at residues 40-50 were firstly formed in the folding process. We also found two potential misfoldings which were caused by the distortion of the local structures at residues 35-37, 45-50.