Thesis (Ph. D.)--University of Delaware, 2007. / Principal faculty advisor: Colin Thorpe, Dept. of Chemistry & Biochemistry. Includes bibliographical references.

Undergraduate honors paper--Mount Holyoke College, 2007. Program in Biochemistry. / Includes bibliographical references (leaves 64-67).

Orientador: Makoto Yoshida / Banca: Valter Luiz Líbero / Banca: João Ruggiero Neto / Resumo: Estudamos o enovelamento de proteínas através da termodinâmica de uma cadeia heteropolimérica. Para isso, adaptamos um método de Monte Carlo introduzido por Wang e Landau para o estudo de transições de fase em sistemas magnéticos para estudarmos a mecânica estatística dessa cadeia. Trata-se de um método que se vale do passeio randômico no espaço de energias para determinação da densidade de estados acessíveis à cadeia e com ela determinar grandezas termodinâmicas do sistema em estudo. Para obtermos essa densidade de estados, adotamos modelos de rede para gerarmos todas as conformações geométricas possíveis de uma cadeia de 27 monômeros em uma rede cúbica. Estudamos várias seqüências de monômeros adotando os modelos de rede mais relevantes utilizados para a investigação do enovelamento de proteínas tais como o modelo HP e modelos mais elaborados que utilizam as interações de Miyazawa-Jernigan entre monômeros. Calculamos diversas grandezas termodinâmicas essenciais para a compreensão do enovelamento de proteínas e com isso mostramos a eficiência do método Wang-Landau. / Abstract: We studied the protein folding through investigating the thermodynamics of a hetero-polymeric chain. For this purpose, a Monte Carlo method introduced by Wang and Landau to study the phase transitions in magnetic systems, was adapted to investigate the statistical mechanics of this chain. The method is based on the random walk in the energy space to determine the density of states of the chain and important thermodynamics quantities. For this purpose, we adopted the lattice model and generate all geometric conformations of a 27-monomer chain in a cubic lattice. We studied several sequences of monomers adopting the most relevant lattice models, such as the HP model and more elaborated models considering the Miyazawa-Jernigan interactions. We computed several thermodynamics quantities to help us to understand the protein folding and show the efficiency of the Wang-Landau method. / Mestre

Submitted in fulfillment of the requirements of the Degree of Master of Technology: Chemistry, Durban University of Technology. 2014. / Peptide folding is a very complicated and dynamic process taking place in all living systems. The understanding of a bioactive conformation of the peptides is very important to understand their biological functions and underlying mechanism of action. However, the high flexible nature of peptides makes this process difficult as they can adopt thousands of conformations within the fraction of a second. The usage of experimental techniques in the characterization process is also limited due to several associated complications including synthesis, isolation and crystallization of peptides. The present computational methodologies, on the other hand, are solid enough to provide detailed complementary information about the intrinsic conformational features of peptides by mimicking their physiological conditions. In the present work, molecular dynamics (MD) computational method was used to explore the configurational space of three Aurein peptides, namely Aurein 2.3, Aurein 2.4 and Aurein 2.5. These peptides are secreted by the amphibian skin when they are exposed to external stimuli. These peptides have been reported to possess anti-cancer and anti-bacterial activity with minimum resistance compared to the available drugs. However, despite their medicinal significance, the precise three dimensional structures of Aurein 2.4 and Aurein 2.5 are not as yet known. First, a validation study was performed on Aurein 2.3 to check the efficiency of the computational protocol. The results obtained revealed the presence of -helicity in all residues of the Aurein 2.3, in accordance with its experimental structure. A similar protocol was further used to explore the conformational profiles of the remaining two peptides (Aurein 2.4 and Aurein 2.5) under implicit and explicit solvent conditions. The results obtained revealed that both these peptides exhibit -helical character in all residues although in varying percentages. The -helical region in the case of Aurein 2.4 was localized predominantly in the central residues extending towards its N-terminal residues, whereas it was flanked by N-terminal and the central residues in Aurein 2.5. However, -helicity was completely absent in the explicit solvents, and the peptides preferred to stay either in -turns or extended forms. Hence, the present work provides comprehensive information about the conformational preferences of Aurein peptides which could lead to a better understanding of their native conformations for future investigations and point the way towards developing their new agonists.

published_or_final_version / Biochemistry / Doctoral / Doctor of Philosophy

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