A COMPUTATIONAL PROTOCOL FOR PROTEIN TERTIARY STRUCTURE REFINEMENT

Abstract

The field of protein structure prediction and modeling has long been researched and a number of softwares have been made available for the same. Although this field is promising, obtaining a model with the same accuracy as a crystal structure is still an unsolved problem and the refinement problem is holding back the performance of many softwares. Thus, the structure refinement of a rough model, to bring it closer to the native structure remains a major challenge. Work on this area has been ongoing for many decades and various methodologies have been used, but no method has emerged as a clear winner. Two major problems were identified in the modeled structures, one being that of loop optimization, as loops are the most variable regions of the protein which generally do not match the template and therefore, require special attention. The other one deals with the presence of steric clashes in the modeled structures, especially the ones obtained using multiple templates for modeling different regions of the protein in the form of patches. In this project, a computational protocol has been developed to tackle the above mentioned problems using ab initio modeling for loop optimization and a final molecular dynamics simulation on the modeled protein structures. This protocol helped decrease the RMSD and remove the steric clashes that are present in the predicted models thereby making them physically plausible.