Distinguishing Biomolecular Pathways and Metastable States
| Autor: | Huan Yang, Vitor B. P. Leite, Antonio B. de Oliveira, Paul C. Whitford |
|---|---|
| Přispěvatelé: | Universidade Estadual Paulista (Unesp), Northeastern Univ, Rice Univ |
| Rok vydání: | 2019 |
| Předmět: |
Quantitative Biology::Biomolecules
Protein Folding 010304 chemical physics Computer science Protein Conformation Energy landscape Folding (DSP implementation) 01 natural sciences Computer Science Applications Visualization src Homology Domains Phase space 0103 physical sciences Metric (mathematics) Projection method Thermodynamics Protein folding Statistical physics Physical and Theoretical Chemistry Representation (mathematics) Staphylococcal Protein A |
| Zdroj: | Web of Science Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| ISSN: | 1549-9626 |
| Popis: | Made available in DSpace on 2020-12-10T19:41:27Z (GMT). No. of bitstreams: 0 Previous issue date: 2019-11-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) NSF CAREER award Center for Theoretical Biological Physics - NSF 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. Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, Dept Fis, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil Northeastern Univ, Dept Phys, Boston, MA 02115 USA Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 USA Univ Estadual Paulista, Inst Biociencias Letras & Ciencias Exatas, Dept Fis, BR-15054000 Sao Jose Do Rio Preto, SP, Brazil FAPESP: 2018/18668-1 FAPESP: 2016/19766-1 FAPESP: 2014/50739-5 NSF CAREER award: MCB-1350312 Center for Theoretical Biological Physics - NSF: PHY-1427654 |
| Databáze: | OpenAIRE |
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