Systematically constructing kinetic transition network in polypeptide from top to down: trajectory mapping.

Molecular dynamics (MD) simulation is an important tool for understanding bio-molecules in microscopic temporal/spatial scales. Besides the demand in improving simulation techniques to approach experimental scales, it becomes more and more crucial to develop robust methodology for precisely and objectively interpreting massive MD simulation data. In our previous work [J Phys Chem B 114, 10266 (2010)], the trajectory mapping (TM) method was presented to analyze simulation trajectories then to construct a kinetic transition network of metastable states. In this work, we further present a top-down implementation of TM to systematically detect complicate features of conformational space. We first look at longer MD trajectory pieces to get a coarse picture of transition network at larger time scale, and then we gradually cut the trajectory pieces in shorter for more details. A robust clustering algorithm is designed to more effectively identify the metastable states and transition events. We applied this TM method to detect the hierarchical structure in the conformational space of alanine-dodeca-peptide from microsecond to nanosecond time scales. The results show a downhill folding process of the peptide through multiple pathways. Even in this simple system, we found that single common-used order parameter is not sufficient either in distinguishing the metastable states or predicting the transition kinetics among these states.