Multi-dimensional scaling and MODELLER-based evolutionary algorithms for protein model refinement

Protein structure prediction, i.e., computationally predicting the three-dimensional structure of a protein from its primary sequence, is one of the most important and challenging problems in bioinformatics. Model refinement is a key step in the prediction process, where improved structures are constructed based on a pool of initially generated models. Since the refinement category was added to the biennial Critical Assessment of Structure Prediction (CASP) in 2008, CASP results show that it is a challenge for existing model refinement methods to improve model quality consistently. This paper presents three evolutionary algorithms for protein model refinement, in which multidimensional scaling(MDS), the MODELLER software, and a hybrid of both are used as crossover operators, respectively. The MDS-based method takes a purely geometrical approach and generates a child model by combining the contact maps of multiple parents. The MODELLER-based method takes a statistical and energy minimization approach, and uses the remodeling module in MODELLER program to generate new models from multiple parents. The hybrid method first generates models using the MDS-based method and then run them through the MODELLER-based method, aiming at combining the strength of both. Promising results have been obtained in experiments using CASP datasets. The MDS-based method improved the best of a pool of predicted models in terms of the global distance test score (GDT-TS) in 9 out of 16test targets.