Replica exchange molecular dynamics simulation of structure variation from α/4β-fold to 3α-fold protein

Replica exchange molecular dynamics (REMD) simulation provides an efficient conformational sampling tool for the study of protein folding. In this study, we explore the mechanism directing the structure variation from alpha/4 beta-fold protein to 3 alpha-fold protein after mutation by conducting REMD simulation on 42 replicas with temperatures ranging from 270 K to 710 K. The simulation began from a protein possessing the primary structure of GA88 but the tertiary structure of GB88, two G proteins with "high sequence identity." Albeit the large C alpha-root mean square deviation (RMSD) of the folded protein (4.34 angstrom at 270 K and 4.75 angstrom at 304 K), a variation in tertiary structure was observed. Together with the analysis of secondary structure assignment, cluster analysis and principal component, it provides insights to the folding and unfolding pathway of 3 alpha-fold protein and alpha/4 beta-fold protein respectively paving the way toward the understanding of the ongoings during conformational variation.