Exploring Constant pH Molecular Dynamics of Proteins in Explicit Solvent

Abstract

Acidity is an important property in determining protein activity and influences of enzymes during reactions in a biological system. How acidic a system is controls the actions of the proteins in it, which is important because proteins are a part of almost all processes within a cell. We used a special type of Molecular Dynamics (MD) called Constant pH Molecular Dynamics (CPHMD) because it takes into account different protonation states, whereas standard MD does not. We used CPHMD to create the amino acid model compounds, aspartic acid, glutamic acid, lysine and histidine, in order to use them in the simulation of a protein (the Hen Egg White Lysozyme). In our simulations the pKa of single amino acids (the building blocks of proteins) and of the residues (amino acids) in the protein are quite similar when compared to experimental values. This is the first documented explicit solvent CPHMD simulation of a full protein. We compared the accuracy of the explicit solvent technique used here with implicit solvent CPHMD simulations. The simulations account for the multiple protonation states of the amino acids, which brings us close to our goal of simulating full protein systems in pH-dependent environments.