Computational investigations of protein denaturation: apomyoglobin and chaotrope-arene interactions

Molecular dynamics (MD) and Monte Carlo (MC) simulations are being used to investigate protein denaturation. The calculations use the AMBER/OPLS force field with explicit representation of the solvent via the TIP3P and TIP4P models of water. The thermal denaturation of apomyoglobin has been followed in two 500 ps MD simulations at 85 °C. The resultant structures provide a detailed model of a molten globule, and close agreement is obtained with experimental data on the helical content of both native apomyoglobin and the low pH folding intermediate. The mechanism of protein denaturation by chaotropic agents is also being pursued. The possibility of direct contact between the chaotropes and aromatic sidechains is supported by MC computations of free energy profiles for the approach of urea and guanidinium ion to aromatic hydrocarbons in water.