Development of Loop Modeling and Sidechain Packing Algorithm for Protein Structure Prediction.

Proteins play crucial roles in almost every biological process. The function of a protein depends on the specific spatial shape that a protein takes in nature. The Protein Structure Prediction problem is to predict the tertiary structure of a protein from its amino acid sequence. Experimental methods (NMR spectroscopy and X-ray crystallography) are slow and expensive. There is an increasing gap between the number of existing protein sequences and that of the known protein structures. Computational methods have the potential to rapidly and effectively annotate these protein sequences. We proposed a new method for loop modeling that uses Weighted Multidimensional Scaling (WMDS), a statistical technique for exploring similarities in data. Using WMDS, a gap is first fitted with suitable loop candidates from database, and later relaxed iteratively to return the loop to its original size. Bioinformatics Solutions Inc (BSI) offers a Protein Structure Modeling solution in RAPTOR packages that contain a loop modeling module called OWL. The loop modeling module OWL uses Cyclic Coordinate Descent (CCD) technique to close a loop. However, we observe that in some uncommon situations, OWL fails to close the gap properly. Successful development and implementation of a better loop closure algorithm will enable BSI to commercialize and market the program as a module of RAPTOR package. This will enhance the functionality of the highly regarded RAPTOR with a better 3D structure prediction module that will eventually help in expanding RAPTOR market among academics and pharmaceutical laboratories.

Mohammad Ziaur Rahman
Faculty Supervisor: 
Dr. Ming Li