| Full text | |
| Author(s): |
Galembeck, Sergio E.
[1]
;
Bickelhaupt, F. Matthias
[2, 3]
;
Guerra, Celia Fonseca
[3]
;
Galembeck, Eduardo
[4]
Total Authors: 4
|
| Affiliation: | [1] FFCLRP USP, Dept Quim, Ribeirao Preto, SP - Brazil
[2] Radboud Univ Nijmegen, Inst Mol & Mat, NL-6525 AJ Nijmegen - Netherlands
[3] Vrije Univ Amsterdam, ACMM, Dept Theoret Chem, NL-1081 HV Amsterdam - Netherlands
[4] IB UNICAMP, Dept Bioquim, Campinas, SP - Brazil
Total Affiliations: 4
|
| Document type: | Journal article |
| Source: | Journal of Molecular Modeling; v. 20, n. 7 JUL 2014. |
| Web of Science Citations: | 2 |
| Abstract | |
Interactions between an inhibitor and amino acids from a binding pocket could help not only to understand the nature of these interactions, but also to support the design of new inhibitors. In this paper, we explore the key interaction between a second generation non-nucleoside reverse transcriptase inhibitor (NNRTI), GW420867X, and HIV-1 RT amino acid Lys101 (K101), by quantum mechanical methods. The neutral, protonated, and zwitterionic complexes of GW420867X-K101 were studied. The interaction energies were determined by SCS-MP2/def2-cc-pVQZ, and the electron density was analyzed by natural bond orbital (NBO), atoms in molecules (AIM) and reduced gradient analysis. A large increase in the interaction was observed with the tautomerization of neutral or neutral protonated species. The monomers interact by two medium-strength hydrogen bonds, one partially covalent and another noncovalent. There are some van der Waals intramolecular interactions that are topologically unstable. The nature of the intermolecular interactions was also analyzed using quantitative molecular orbital (MO) theory in combination with an energy decomposition analysis (EDA) based on dispersion-corrected density functional theory (DFT) at BLYP-D/TZ2P. (AU) | |
| FAPESP's process: | 08/02677-0 - Computational Study of the interaction between HIV-1 reverse transcriptase non-nucleoside inhibitors with amino acids of the inhibitory site |
| Grantee: | Sergio Emanuel Galembeck |
| Support Opportunities: | Regular Research Grants |