A wavelet approach for the analysis of folding trajectory of protein Trp-cage

Abstract

Understanding how protein folds into a functional native structure is arguably one of the most challenging problems remaining in computational biology. Currently, the protein folding mechanism is often characterized by calculating the free energy landscape in terms of various reaction coordinates such as the fraction of native contacts, the radius of gyration, the RMS deviation from the native and so on. In this paper, we present a wavelet approach towards understanding the global state changes during protein folding. The approach is based on the wavelet analysis on the trajectories of various reaction coordinates to identify the significant intermediate states or structural motifs in the folding process. We demonstrate through an example protein Trp-cage that this approach extracts crucial information about protein folding intermediate states as well as the time correlation among these states. Furthermore, the current approach reveals a meaningful structural pattern that had been overlooked in previous works, which provides a better understanding of the folding mechanism as well as the limitation of the current force fields. © Imperial College Press.