Ami Levy-Moonshine1, El-Ad David Amir, Chen Keasar. 1. Department of Computer Science and Department of Life Sciences, Ben-Gurion University of the Negev, 84105 Beer-Sheva, Israel.
Abstract
MOTIVATION: The roughness of energy landscapes is a major obstacle to protein structure prediction, since it forces conformational searches to spend much time struggling to escape numerous traps. Specifically, beta-sheet formation is prone to stray, since many possible combinations of hydrogen bonds are dead ends in terms of beta-sheet assembly. It has been shown that cooperative terms for backbone hydrogen bonds ease this problem by augmenting hydrogen bond patterns that are consistent with beta sheets. Here, we present a novel cooperative hydrogen-bond term that is both effective in promoting beta sheets and computationally efficient. In addition, the new term is differentiable and operates on all-atom protein models. RESULTS: Energy optimization of poly-alanine chains under the new term led to significantly more beta-sheet content than optimization under a non-cooperative term. Furthermore, the optimized structure included very few non-native patterns. AVAILABILITY: The new term is implemented within the MESHI package and is freely available at http://cs.bgu.ac.il/ approximately meshi.
MOTIVATION: The roughness of energy landscapes is a major obstacle to protein structure prediction, since it forces conformational searches to spend much time struggling to escape numerous traps. Specifically, beta-sheet formation is prone to stray, since many possible combinations of hydrogen bonds are dead ends in terms of beta-sheet assembly. It has been shown that cooperative terms for backbone hydrogen bonds ease this problem by augmenting hydrogen bond patterns that are consistent with beta sheets. Here, we present a novel cooperative hydrogen-bond term that is both effective in promoting beta sheets and computationally efficient. In addition, the new term is differentiable and operates on all-atom protein models. RESULTS: Energy optimization of poly-alanine chains under the new term led to significantly more beta-sheet content than optimization under a non-cooperative term. Furthermore, the optimized structure included very few non-native patterns. AVAILABILITY: The new term is implemented within the MESHI package and is freely available at http://cs.bgu.ac.il/ approximately meshi.
Authors: H M Berman; J Westbrook; Z Feng; G Gilliland; T N Bhat; H Weissig; I N Shindyalov; P E Bourne Journal: Nucleic Acids Res Date: 2000-01-01 Impact factor: 16.971