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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Distinguishing Biomolecular Pathways and Metastable States

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Oliveira, Jr., Antonio B. [1] ; Yang, Huan [2] ; Whitford, Paul C. [2] ; Leite, Vitor B. P. [3, 1]
Número total de Autores: 4
Afiliação do(s) autor(es):
[1] Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, Dept Fis, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Northeastern Univ, Dept Phys, Boston, MA 02115 - USA
[3] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 15, n. 11, p. 6482-6490, NOV 2019.
Citações Web of Science: 1

Protein folding occurs in a high dimensional phase space, and the representation of the associated energy landscape is nontrivial. A widely applied approach to studying folding landscapes is to describe the dynamics along a small number of reaction coordinates. However, other strategies involve more elaborate analysis of the complex phase space. There have been many attempts to obtain a more detailed representation of all available conformations for a given system. In this work, we address this problem using a metric based on internal distances between amino acids to describe the differences between any two conformations. Using an effective projection method, we are able to go beyond the typical one-dimensional representation and provide intuitive two dimensional visualizations of the landscape. We refer to this method as the energy landscape visualization method (ELViM). We have applied this methodology using a C-alpha structure-based model to study the folding of two well-known proteins: SH3 domain and protein-A. Our visualization method yields a detailed description of the folding process, making possible the identification of transition state regions, and establishing the paths that lead to the native state. For SH3, we have analyzed structural differences in the distribution of folding routes. The competition between the native and mirror structures in protein A is also discussed. Finally, the method is applied to study conformational changes in the protein elongation factor thermally unstable. Distinct features of ELViM are that it does not require or assume a reaction coordinate, and it does not require analysis of kinetic aspects of the system. (AU)

Processo FAPESP: 16/19766-1 - Relevo de superfícies de energia de macromoléculas biológicas com aplicações em biotecnologia e em biomedicina
Beneficiário:Vitor Barbanti Pereira Leite
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/50739-5 - Elucidating the role of disorder during biomolecular fuction
Beneficiário:Vitor Barbanti Pereira Leite
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 18/18668-1 - Visualização do relevo de superfícies de energia de macromoléculas biológicas
Beneficiário:Vitor Barbanti Pereira Leite
Modalidade de apoio: Bolsas no Exterior - Pesquisa