Energy landscape and global optimization for a frustrated model protein

Abstract

The three-color (BLN) 69-residue model protein was designed to exhibit frustrated folding. We investigate the energy landscape of this protein using disconnectivity graphs and compare it to a Gō model, which is designed to reduce the frustration by removing all non-native attractive interactions. Finding the global minimum on a frustrated energy landscape is a good test of global optimization techniques, and we present calculations evaluating the performance of basin-hopping and genetic algorithms for this system. Comparisons are made with the widely studied 46-residue BLN protein. We show that the energy landscape of the 69-residue BLN protein contains several deep funnels, each of which corresponds to a different β-barrel structure. © 2011 American Chemical Society.