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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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

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Author(s):
da Silva, Fernando B. [1] ; de Oliveira, Vinicius M. [2] ; Sanches, Murilo N. [1] ; Contessoto, Vinicius G. [3, 4] ; Leite, Vitor B. P. [1]
Total Authors: 5
Affiliation:
[1] Sao Paulo State Univ, UNESP, Inst Biosci Humanities & Exact Sci, Dept Phys, BR-15054000 Sao Jose Do Rio Preto, SP - Brazil
[2] Brazilian Ctr Res Energy & Mat, Brazilian Biosci Natl Lab, LNBio CNPEM, BR-13083970 Campinas, SP - Brazil
[3] Rice Univ, Ctr Theoret Biol Phys, Houston, TX 77005 - USA
[4] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biorenewables Natl Lab LNBR, BR-13083100 Campinas, SP - Brazil
Total Affiliations: 4
Document type: Journal article
Source: JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 60, n. 2, p. 982-988, FEB 2020.
Web of Science Citations: 1
Abstract

Rational 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 C alpha 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. (AU)

FAPESP's process: 16/19766-1 - Biological macromolecules energy landscapes with applications in biotechnology and in biomedicine
Grantee:Vitor Barbanti Pereira Leite
Support type: 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 type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/09662-7 - Rational Evolution by Computational Methods Applied in Enzymes Related to Bioethanol Production
Grantee:Vinícius de Godoi Contessoto
Support type: Scholarships abroad - Research Internship - Post-doctor
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 type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/25130-5 - Comparison of non-specific potentials with structure-based potentials in protein folding
Grantee:Murilo Nogueira Sanches
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/18668-1 - Biological macromolecules energy landscapes visualization
Grantee:Vitor Barbanti Pereira Leite
Support type: Scholarships abroad - Research