Methodological procedures of Molecular Dynamics Simulated Annealing for the chain folding of the flexible tetrapeptide Boc-Gly-Leu-Gly-Gly-NMe with analysis of the evolution mechanism

Abstract

Methodological criteria and procedures of Molecular Dynamics Simulated Annealing (SA) were developed for the chain folding of the elastin tetrapeptide Boc-Gly-Leu-Gly-Gly-NMe into the conformational Global Minimum (GM), starting from the all-extended structure. The mechanism of the folding evolution was analyzed. SA is a slow dissipative process showing a complex dependence on the control parameters with competing attractor points and evolution toward the GM as the most probable result. The annealing process is independent of the heating set-up procedures and temperature of the initial excited state provided that the system is fully activated (i.e. the initial energy and dissipation energy rate is such that practically any energy well on the potential surface is allowed during the decay process). A temperature of 500 K is approximately the lowest initial temperature for a working annealing process. Moreover, it is possible to reach the GM by annealing processes to room temperature. The time constant that controls the energy-dissipation rate has been parametrically varied for annealing processes showing ordered and disordered behaviors. Generally, there are lower and upper bounds for the cooling rate outside of which the annealed solutions become unstable with sensitive dependence on the process conditions; conversely, between them there are stable attractor regions. The annealing mechanism has been analyzed in-depth by considering a damped, non-linear, monodimensional oscillator moving on a multiple-minima potential for modeling of the annealing process. The decay toward the most stable attractor point has been interpreted by means of the competing attractors and its attractor basins in the phase (velocity-position) space of the system.