Statistical thermodynamics of protein microstates: An investigation of denatured state thermodynamics, M-values, and protein thermostability

Proteins are macromolecules composed of amino acids and are responsible for most functions in living cells. Environmental agents and endogenous metabolic processes can cause chemical modifications to DNA. These modifications can result in mutations that translate to the protein level. Mutations are important for the evolution of organisms but they can also be harmful and cause human diseases. With this in mind, years of research have led to a greater understanding of the structure, thermodynamics, and the activity of many proteins.; Even with thousands of man years devoted toward the understanding of protein science, many mysteries remain. The work that follows addresses some of the unresolved issues in protein science. One of the first issues addressed in this dissertation centers around the energies of alternative conformations in the unfolded state of proteins. Proteins fold into a three dimensional structure to function. Although there is a plethora of information about the folded state of proteins, only recently has our understanding about the nature of the unfolded state become more clear.; A protein will fold from the unfolded state into the folded state structure. This transition can be optically monitored. Some of the assumptions made while analyzing this transition are also investigated in this work. Statistically the native state is considered as an ensemble of inter-converting conformational fluctuations. The nature of these fluctuations are investigated as well as the effect of mutations on the inherent communication network in a protein structure. Proteins derived from organisms that live at different temperature environments are studied in order to arrive at a better understanding about how mutations affect the network of communication. This may aid the design process for protein therapeutics.