Procesos físicos en sistemas biomoleculares : plegamiento de la deca-alanina desde una conformación aleatoria hasta su estructura nativa de hélice alfa.

Abstract

The protein folding process of the deca-alanine system in water was studied through molecular dynamics simulations. The potential of mean force PMF associated with the transition, along the reaction coordinate ξ, was determined by sampling the structures adopted by the system. The initial sample of structures was generated by performing a targeted molecular dynamics simulation (SMD) along the z-axis for 1 [ns]. Based on the information obtained from this simulation a cluster analysis to identify the structures that defined the windows for Umbrella sampling. The reaction coordinate ξ was defined as the end-to-end distance, or z-elongation, of the polypeptide. Application of a bias harmonic potential kept the sampling confined to the vicinity of each sampling window. The potential of mean force calculated by the weighted histogram analysis method (WHAM), disclosed the existence of a potential barrier of height 4.02 [kcal/mol] and width ∆ξ =12 [A]. The barrier was found to be demarcated by two interesting minimals, a global minimum at ξ =13.7 [A] and a very pronounced local minimum at ξ =15.7 [A]. These energetic features are typical of the folding process and are associated with the existence of the native alpha-helix conformation of the polypeptide and a low-energy unfolded conformation.