Non-Native Cooperative Interactions Modulate Protein Folding Rates

Author(s)

da Silva, Fernando Bruno ^[1] ; Contessoto, Vinicius G. ^[2] ; de Oliveira, Vinicius M. ^[1] ; Clarke, Jane ^[3] ; Leite, Vitor B. P. ^[1]

Affiliation

^[1] Sao Paulo State Univ, Inst Biosci Humanities & Exact Sci, Dept Phys, UNESP, BR-15054000 Sao Paulo - Brazil

^[2] Brazilian Bioethanol Sci & Technol Lab CTBE, BR-13083100 Campinas, SP - Brazil

^[3] Univ Cambridge, Dept Chem, Lensfield Rd, Cambridge CB2 1EW - England

• Document type: Journal article
• Source: Journal of Physical Chemistry B; v. 122, n. 48, p. 10817-10824, DEC 6 2018.
• Web of Science Citations: 3

Abstract

The energy landscape theory and the funnel description have had remarkable success in describing protein folding mechanisms and function. However, there are experimental results that are not understood using this approach. Among the puzzling examples are the alpha-spectrin results, in which the R15 domain folds 3 orders of magnitude more rapidly than the homologous R16 and R17, even though they are structurally very similar to each other. Such anomalous observations are usually attributed to the influence of internal friction on protein folding rates, but this is not a satisfactory explanation. In this study, this phenomenon is addressed by focusing on non-native interactions that could account for this effect. We carried out molecular dynamics simulations with structure-based C(alpha )models, in which the folding process of alpha-spectrin domains was investigated. The simulations take into account the hydrophobic and electrostatic contributions separately. The folding time results have shown qualitative agreement with the experimental data. We have also investigated mutations in R16 and R17, and the simulation folding time results correlate with the observed experimental ones. We suggest that the origin of the internal friction, at least in this case, might emerge from a cooperativity effect of these non-native interactions. (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: 16/13998-8 - Rational evolution by computational methods applied to predict mutations in enzymes to biofuels production
• Grantee: Vinícius de Godoi Contessoto
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• FAPESP's process: 17/09662-7 - Rational Evolution by Computational Methods Applied in Enzymes Related to Bioethanol Production
• Grantee: Vinícius de Godoi Contessoto
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor
• FAPESP's process: 14/06862-7 - Computational studies in protein folding and enzymes engineering involved in bioethanol production
• Grantee: Vitor Barbanti Pereira Leite
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/11614-3 - Effect of pH and Cancer-Activating Mutations on Functional Transition of Estrogen Receptor
• Grantee: Vinicius Martins de Oliveira
• Support Opportunities: Scholarships in Brazil - Post-Doctoral