Rational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactions

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dc.contributor.authorB. Da Silva, Fernando [UNESP]
dc.contributor.authorM. De Oliveira, Vinícius
dc.contributor.authorSanches, Murilo N. [UNESP]
dc.contributor.authorContessoto, Vinícius G.
dc.contributor.authorLeite, Vitor B. P. [UNESP]
dc.contributor.institutionUniversidade Estadual Paulista (Unesp)
dc.contributor.institutionLNBio/CNPEM
dc.contributor.institutionCNPEM
dc.contributor.institutionRice University
dc.date.accessioned2020-12-12T01:10:09Z
dc.date.available2020-12-12T01:10:09Z
dc.date.issued2020-02-24
dc.description.abstractRational design of proteins via mutagenesis is crucial for several biotechnological applications. A significant challenge of the computational strategies used to predict optimized mutations is to understand the influence of each amino acid during the folding process. In the present work, chymotrypsin inhibitor 2 (CI2) and several of its designed mutants have been simulated using a non-native hydrophobic and electrostatic potential as a structure-based Cα model. Through these simulations, we could identify the most critical folding stage to accelerate CI2 and also the charged residues responsible for providing its thermostability. The replacement of ionizable residues for hydrophobic ones tended to promote the formation of the CI2 secondary structure in the early transition state, which speeds up folding. However, this same replacement destabilized the native structure, and there was a decrease in the protein thermostability. Such a simple method proved to be capable of providing valuable information about thermodynamics and kinetics of CI2 and its mutations, thus being a fast alternative to the study of rational protein design.en
dc.description.affiliationDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)
dc.description.affiliationBrazilian Biosciences National Laboratory Brazilian Center for Research in Energy and Materials LNBio/CNPEM
dc.description.affiliationBrazilian Biorenewables National Laboratory LNBR Brazilian Center for Research in Energy and Materials CNPEM
dc.description.affiliationCenter for Theoretical Biological Physics Rice University
dc.description.affiliationUnespDepartment of Physics Institute of Biosciences Humanities and Exact Sciences São Paulo State University (UNESP)
dc.format.extent982-988
dc.identifierhttp://dx.doi.org/10.1021/acs.jcim.9b00911
dc.identifier.citationJournal of Chemical Information and Modeling, v. 60, n. 2, p. 982-988, 2020.
dc.identifier.doi10.1021/acs.jcim.9b00911
dc.identifier.issn1520-5142
dc.identifier.issn1549-9596
dc.identifier.scopus2-s2.0-85077220845
dc.identifier.urihttp://hdl.handle.net/11449/198341
dc.language.isoeng
dc.relation.ispartofJournal of Chemical Information and Modeling
dc.sourceScopus
dc.titleRational Design of Chymotrypsin Inhibitor 2 by Optimizing Non-Native Interactionsen
dc.typeArtigo
unesp.author.orcid0000-0002-0285-8700[1]
unesp.author.orcid0000-0003-0927-3825[2]
unesp.author.orcid0000-0002-1891-9563 0000-0002-1891-9563[4]
unesp.author.orcid0000-0003-0008-9079[5]

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