Conformational search of Proteins and Protein Loops

Abstract

This thesis focuses on understanding the structure and dynamics of proteins using simulations. The main system of interest in our case was cytochrome b5, an electron transport protein, which exists in both Microsomal and Outer Mitochondrial isoforms. We conducted 20 ns Molecular Dynamics simulations of apocytochrome b5 (protein without the heme group). The apocytochrome b5 proteins were more flexible than the holo proteins and the effect of heme removal was mostly confined to the heme-binding (core 1) region.The second part of my thesis consisted of performing replica exchange simulations of the holo proteins. About 4.4 ns simulations of the proteins were conducted with 12 replicas spanning 320 K-450 K using the GB/SA implicit solvent model. The rat Microsomal protein exhibited larger RMS Deviations from the starting structure as compared to the rat OM protein