PH-Based Molecular Dynamics Simulation for Analysing Protein Structure and Folding

Abstract

The structure and function of a protein are influenced by environmental factors like pH, temperature, salt concentrations, etc. The intrinsic dynamics of a protein in such environments involve temporal and spatial changes at the atomic level. These changes can be understood with the help of molecular dynamics (MD) simulations. This chapter concentrates on the MD simulation of proteins at constant pH, allowing researchers to bridge the gap. The constant pH approach accounts for the protonation states of the amino acid residues in a protein while receiving little or no inputs from the forcefields employed for the simulation. Once completed, the simulations provide valuable data on the folding process of a protein and the free energy of binding between the protein and other interacting molecules (another protein, ligand, DNA, etc.). The chapter introduces the concept of constant pH simulation and the effect of pH on each amino acid. The effect of the pH environment on the spatiotemporal arrangement of the proteins and the presence of intermediate states have been discussed. We then provide insights into the practical aspects of the all-atom simulation of the constant pH approach and the analysis of the trajectories using the MD simulation data. Case studies are provided to help understand the nuances of different MD simulation systems and how they vary. In the end, we discuss the future directions to further research in this area and achieve MD simulation results with higher accuracy and reliability.