Identifying Metastable States of Folding Proteins

Recent molecular dynamics simulations of biopolymers have shown that in many cases the global features of the free energy landscape can be characterized in terms of the metastable conformational states of the system. To identify these states, a conceptionally and computationally simple approach is proposed. It consists of (i) an initial preprocessing via principal component analysis to reduce the dimensionality of the data, followed by k-means clustering to generate up to 10(4) microstates, (ii) the most probable path algorithm to identify the metastable states of the system, and (iii) boundary corrections of these states via the introduction of cluster cores in order to obtain the correct dynamics. By adopting two well-studied model problems, hepta-alanine and the villin headpiece protein, the potential and the performance of the approach are demonstrated.