| Full text | |
| 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 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: | 17/25130-5 - Comparison of non-specific potentials with structure-based potentials in protein folding |
| Grantee: | Murilo Nogueira Sanches |
| Support Opportunities: | Scholarships in Brazil - Scientific Initiation |
| 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: | 18/18668-1 - Biological macromolecules energy landscapes visualization |
| Grantee: | Vitor Barbanti Pereira Leite |
| Support Opportunities: | Scholarships abroad - Research |