Proteins in Vacuo : Molecular dynamics studies of hen egg white lysozyme submitted to unfolding and relaxation conditions

Abstract: Electrically neutral and charged lysozyme molecules were studied with molecular dynamics (MD) techniques. Denaturation and renaturation conditions were simulated for the system in vacuo. Experimental observations of biomolecules in vacuo were related to the conformational space accessible under unfolding-relaxation conditions. The native form of lysozyme and a disulfide reduced form were both submitted to two types of unfolding perturbations: i) centrifugal forces, and ii) Coulombic repulsion. Some of the obtained conformations compared well with compact and extended conformations found in gasphase experiments under different conditions.Additionally, intermediates isolated from the centrifugal unfolding runs of lysozyme in vacuo, were relaxed by removing the applied perturbation. A series of renaturationlike simulations were carried out. The richness of structural elements found in the conformational space of the relaxed molecules permits discussing some aspects of the folding problem. The simulation results on disulfide-intact and disulfide-reduced lysozyme models suggest that lysozyme undergoes a folding process in vacuo.