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

Autor(es)

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]}

Afiliação do(s) autor(es)

^[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

• Tipo de documento: Artigo Científico
• Fonte: JOURNAL OF CHEMICAL THEORY AND COMPUTATION; v. 16, n. 1, p. 765-772, JAN 2020.
• Citações Web of Science: 0

Resumo

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)

• 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: 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
• Processo FAPESP: 18/11614-3 - Efeito de Mutações Câncer-Ativadoras e de pH na Transição Funcional do Receptor de Estrógeno
• Beneficiário: Vinicius Martins de Oliveira
• Modalidade de apoio: Bolsas no Brasil - Pós-Doutorado
• Processo FAPESP: 18/01841-2 - Estudo por Simulação Computacional da Interação entre Polieletrólitos e Macromoléculas
• Beneficiário: Sidney Jurado de Carvalho
• Modalidade de apoio: Auxílio à Pesquisa - Regular