Inhibitor docking screened by the modified SAFE_p scoring function : application to cyclic urea HIV-1 PR inhibitors
(c) 2007 Wiley Periodicals, Inc.
| Veröffentlicht in: | Journal of computational chemistry. - 1984. - 28(2007), 13 vom: 05. Okt., Seite 2216-25 |
|---|---|
| 1. Verfasser: | |
| Weitere Verfasser: | , |
| Format: | Aufsatz |
| Sprache: | English |
| Veröffentlicht: |
2007
|
| Zugriff auf das übergeordnete Werk: | Journal of computational chemistry |
| Schlagworte: | Journal Article Amino Acids Azepines HIV Protease Inhibitors SD 146 cyclic urea XK 216 XK 263 XV 638 Urea 8W8T17847W mehr... |
| Zusammenfassung: | (c) 2007 Wiley Periodicals, Inc. Our laboratory has in the past developed a method for the prediction of ligand binding free energies to proteins, referred to as SAFE_p (Solvent free energy predictor). Previously, we have applied this protocol for the prediction of the binding free energy of peptidic and cyclic urea HIV-1 PR inhibitors, whose X-ray structures bound to enzyme are known. In this work, we present the first account of a docking simulation, where the ligand conformations were screened and inhibitor ranking was predicted on the basis of a modified SAFE_p approach, for a set of cyclic urea-HIV-1 PR complexes whose structures are not known. We show that the optimal dielectric constant for docking is rather high, in line with the values needed to reproduce some protein residue properties, like pKa's. Our protocol is able to reproduce most of the observed binding ranking, even in the case that the components of the equation are not fitted to experimental data. Partition of the binding free energy into pocket and residue contributions sheds light into the importance of the inhibitor's fragments and on the prediction of "hot spots" for resistance mutations |
|---|---|
| Beschreibung: | Date Completed 16.10.2007 Date Revised 09.12.2020 published: Print Citation Status MEDLINE |
| ISSN: | 1096-987X |