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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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]
Total Authors: 4
[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
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 15, n. 11, p. 6482-6490, NOV 2019.
Web of Science Citations: 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)

FAPESP's process: 16/19766-1 - Biological macromolecules energy landscapes with applications in biotechnology and in biomedicine
Grantee:Vitor Barbanti Pereira Leite
Support Opportunities: Regular Research Grants
FAPESP's process: 14/50739-5 - Elucidating the role of disorder during biomolecular fuction
Grantee:Vitor Barbanti Pereira Leite
Support Opportunities: Regular Research Grants
FAPESP's process: 18/18668-1 - Biological macromolecules energy landscapes visualization
Grantee:Vitor Barbanti Pereira Leite
Support Opportunities: Scholarships abroad - Research