pH and Charged Mutations Modulate Cold Shock Protein Folding and Stability: A Constant pH Monte Carlo Study

Author(s)

de Oliveira, Vinicius M. ^[1] ; Caetano, Daniel L. Z. ^[2] ; da Silva, Fernando B. ^[2] ; Mouro, Paulo R. ^[2] ; de Oliveira, Jr., Antonio B. ^[2] ; de Carvalho, Sidney J. ^[2] ; Leite, Vitor B. P. ^{[3, 2]}

Affiliation

^[1] Brazilian Biosci Natl Lab, Natl Ctr Res Energy & Mat, LNBio CNPEM, BR-13083970 Campinas, SP - Brazil

^[2] Sao Paulo State Univ UNESP, Inst Biosci Humanities & Exact Sci, Dept Phys, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil

^[3] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA

• Document type: Journal article
• Source: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 16, n. 1, p. 765-772, JAN 2020.
• Web of Science Citations: 0

Abstract

The folding and stability of proteins is a fundamental problem in several research fields. In the present paper, we have used different computational approaches to study the effects caused by changes in pH and for charged mutations in cold shock proteins from Bacillus subtilis (Bs-CspB). First, we have investigated the contribution of each ionizable residue for these proteins to their thermal stability using the TKSA-MC, a Web server for rational mutation via optimizing the protein charge interactions. Based on these results, we have proposed a new mutation in an already optimized Bs-CspB variant. We have evaluated the effects of this new mutation in the folding energy landscape using structure-based models in Monte Carlo simulation at constant pH, SBM-CpHMC. Our results using this approach have indicated that the charge rearrangements already in the unfolded state are critical to the thermal stability of Bs-CspB. Furthermore, the conjunction of these simplified methods was able not only to predict stabilizing mutations in different pHs but also to provide essential information about their effects in each stage of protein folding. (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: 18/18668-1 - Biological macromolecules energy landscapes visualization
• Grantee: Vitor Barbanti Pereira Leite
• Support Opportunities: Scholarships abroad - Research
• 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
• FAPESP's process: 18/01841-2 - Computational Simulation Studies on the Interaction Between Polyelectrolytes and Macromolecules
• Grantee: Sidney Jurado de Carvalho
• Support Opportunities: Regular Research Grants