| Full text | |
| Author(s): |
Pereira, Ander Francisco
;
Martinez, Leandro
Total Authors: 2
|
| Document type: | Journal article |
| Source: | JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 64, n. 8, p. 10-pg., 2024-04-03. |
| Abstract | |
The B domain of protein A (BdpA), a small three-helix bundle, folds on a time scale of a few microseconds with heterogeneous native and unfolded states. It is widely used as a model for understanding protein folding mechanisms. In this work, we use structure-based models (SBMs) and atomistic simulations to comprehensively investigate how BdpA folding is associated with the formation of its secondary structure. The energy landscape visualization method (ELViM) was used to characterize the pathways that connect the folded and unfolded states of BdpA as well as the sets of structures displaying specific ellipticity patterns. We show that the native state conformational diversity is due mainly to the conformational variability of helix I. Helices I, II, and III occur in a weakly correlated manner, with Spearman's rank correlation coefficients of 0.1539 (I and II), 0.1259 (I and III), and 0.2561 (II and III). These results, therefore, suggest the highest cooperativity between helices II and III. Our results allow the clustering of partially folded structures of folding of the B domain of protein A on the basis of its secondary structure, paving the way to an understanding of environmental factors in the relative stability of the basins of the folding ensemble, which are illustrated by the structural dependency of the protein hydration structures, as computed with minimum-distance distribution functions. (AU) | |
| FAPESP's process: | 10/16947-9 - Correlations between dynamics, structure and function in protein: computer simulations and algorithms |
| Grantee: | Leandro Martinez |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 20/04549-0 - Solvent effects on protein folding thermodynamics |
| Grantee: | Ander Francisco Pereira |
| Support Opportunities: | Scholarships in Brazil - Doctorate |
| FAPESP's process: | 18/14274-9 - Protein Structure Determination from Distance Constraints Derived from Chemical Cross-linking: Computational Methods and Applications |
| Grantee: | Leandro Martinez |
| Support Opportunities: | Regular Research Grants |
| FAPESP's process: | 18/24293-0 - Computational methods in optimization |
| Grantee: | Sandra Augusta Santos |
| Support Opportunities: | Research Projects - Thematic Grants |
| FAPESP's process: | 13/08293-7 - CCES - Center for Computational Engineering and Sciences |
| Grantee: | Munir Salomao Skaf |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |