| Full text | |
| Author(s): |
Total Authors: 2
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| Affiliation: | [1] Univ Sao Paulo, Inst Quim, Dept Biochem, BR-05508900 Sao Paulo - Brazil
Total Affiliations: 1
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| Document type: | Journal article |
| Source: | JOURNAL OF CHEMICAL INFORMATION AND MODELING; v. 54, n. 8, p. 2309-2319, AUG 2014. |
| Web of Science Citations: | 7 |
| Abstract | |
Accurate calculations of free energies involved in small-molecule binding to a receptor are challenging. Interactions between ligand, receptor, and solvent molecules have to be described precisely, and a large number of conformational microstates has to be sampled, particularly for ligand binding to a flexible protein. Linear interaction energy models are computationally efficient methods that have found considerable success in the prediction of binding free energies. Here, we parametrize a linear interaction model for implicit solvation with coefficients adapted by ligand and binding site relative polarities in order to predict ligand binding free energies. Results obtained for a diverse series of ligands suggest that the model has good predictive power and transferability. We also apply implicit ligand theory and propose approximations to average contributions of multiple ligand-receptor poses built from a protein conformational ensemble and find that exponential averages require proper energy discrimination between plausible binding poses and false-positives (i.e., decoys). The linear interaction model and the averaging procedures presented can be applied independently of each other and of the method used to obtain the receptor structural representation. (AU) | |
| FAPESP's process: | 11/04354-6 - Computational study on the role of protein flexibility in the recognition of small molecules |
| Grantee: | Ariane Ferreira Nunes Alves |
| Support Opportunities: | Scholarships in Brazil - Master |
| FAPESP's process: | 12/02501-4 - Computer simulation and spectroscopic analysis of proteins involved in bioenergetics and in molecular recognition |
| Grantee: | Guilherme Menegon Arantes |
| Support Opportunities: | Regular Research Grants |