Genetic algorithm feature-based resampling for protein structure prediction

Abstract

Proteins carry out the majority of functionality on a cellular level. Computational protein structure prediction (PSP) methods have been introduced to speed up the PSP process due to manual methods, like nuclear magnetic resonance (NMR) and x-ray crystallography (XC) taking numerous months even years to produce a predicted structure for a target protein. A lot of work in this area is focused on the type of search strategy to employ. Two popular methods in the literature are: Monte Carlo based algorithms and Genetic Algorithms. Genetic Algorithms (GA) have proven to be quite useful in the PSP field, as they allow for a generic search approach, which alleviates the need to redefine the search strategies for separate sequences. They also lend themselves well to feature-based resampling techniques. Feature-based resampling works by taking previously computed local minima and combining features from them to create new structures that are more uniformly low in free energy. In this work we present a feature-based resampling genetic algorithm to refine structures that are outputted by PSP software. Our results indicate that our approach performs well, and produced an average 9.5% root mean square deviation (RMSD) improvement and a 17.36% template modeling score (TM-Score) improvement.