COMPARATIVE CHAINS DYNAMICS OF TRIOSEPHOSPHATE ISOMERASE INVESTIGATED BY MOLECULAR DYNAMICS SIMULATION

Abstract

Triosephosphate isomerase is an enzyme which catalyzes the inter-conversion between glyceraldehyde-3-phosphate and dihydroxyacetone phosphate in the fifth step of the glycolytic pathway. In this study, molecular dynamics simulation technique was employed to investigate the dynamics of the two monomer chains of triosephosphate isomerase of trypanosoma brucei brucei (TbTIM) using GROMACS 2016.04 software. The MD simulation of the x-ray structure of TbTIM was performed using the GROMOS 9643a1 force field and simple point charge water model under isothermal-isobaric condition with periodic boundary conditions imposed on x, y, z directions. The Root Mean Square Deviation (RMSD) Root Mean Square fluctuation (RMSF), Radius of Gyration (ROG), Solvent accessible surface area (SASA) and hydrogen bonds were computed. The RMSD values indicate that chain-B shows transition between two conformational states with higher RMSD value of 0.45 nm when compared to chain-A with RMSD of 0.27 nm. The RMSF values indicates that residues of loop 6 (residues 166 to 177) have the highest fluctuations in both chains compared to other residues with chain-A having higher fluctuations peak. The ROG values of chain-A varies from 1.675 nm to 1.761 nm while that of chain-B varies from 2.480 nm to 2.590 nm implying that chain-A is more compact during the simulation than chain-B. The SASA values indicates that chain-B has more contact with solvent than chain-A. 160 hydrogen bonds were found which indicates the stability of the protein during the simulation. From the RMSD, ROG, SASA values, it is evident that chain-B of triosephosphate isomerase of trypanosoma bruceibrucei displayed greater structural dynamics than chain-A during the MD simulation.