| The subject of this thesis is the study of the conformational equilibria of the polypeptide chain. First we review major approaches to the protein folding problem (chapter 1)--the question of how a protein chain reaches its biologically active conformation. We then present an analytical study of the conformational preferences in a polypeptide (chapter 2). We study the coexistence of different types of helices--one of the prevalent local polypeptide structures. Our findings suggest that a certain type of helical conformation, the 3{dollar}sb{lcub}10{rcub}{dollar} helix, may play a significant role in the formation and stabilization of helical structure.; In chapter 3 we use molecular dynamics simulation methods with an atomic-level model of a solvated protein to characterize the equilibrium structure and conformational dynamics of the small protein, segment B1 of streptococcal protein G(GB1). We describe equilibrium properties of the protein and establish that the model that we employ describes a stable conformation, conforming to the experimental data on the protein's structure and dynamics under native conditions. We also suggest that our description of the native state as a conformational manifold rationalizes differences between NMR- and X-ray determined structures of this protein.; Finally, we investigate the folding mechanism and thermodynamics of GB1 (chapter 4). We study folding by the characterization of non-native states of the protein, which coexist with the native manifold under folding conditions. We construct free energy surfaces along several parameters discriminating between native and non-native conformations, and use them to analyze the folding process. We relate our findings to general theories of how small proteins may fold and formulate a hypothesis on the involvement of solvent in protein folding.; Thesis concludes with an epilogue (chapter 5), where we summarize the results of theoretical studies presented here and discuss their relation to experiment. |
