THE PROTEIN DYNAMICAL TRANSITION IN LYSOZYME POWDER: A COMPUTATIONAL STUDY

Abstract

Understanding the low-temperature behavior of protein powders is important for the storage and handling of lyophilized protein products, such as pharmaceuticals. The protein dynamical transition (PDT) is a phenomenon where the protein dynamics experiences a sudden increase at a temperature TD. The activation at TD is preceded by another activation of motions at a lower temperature (Tlow). The transitions at TD and Tlow are believed to be related to the solvent’s motion and the onset of methyl group rotations, respectively. Despite the abundance of experimental and computational studies on this subject, the cause of the PDT and the detailed mechanism of how the protein and water motions are a↵ected are still missing, especially at the microscopic level. This thesis uses molecular simulations to provide the first microscopic picture of the correlation between local water dynamics and protein motions and their connection to the PDT. Furthermore, it identifies an amplification in the rotations about single bonds and ring flips in the side chains that the transition at Tlow can be directly attributed to. In contrast to the previous studies, the onset of methyl group rotations is found to not be concurrent with the activation of side chain motions seen at Tlow.