Please use this identifier to cite or link to this item:
Title: Creating a high-throughput screening database to propose ligands capable of modulating the HIV-1 protease receptor
Authors: Micallef, Chantelle
Shoemake, Claire
Azzopardi, Lilian M.
Keywords: High throughput screening (Drug development)
Protein drugs -- Analysis
HIV (Viruses)
AIDS (Disease)
Issue Date: 2013
Publisher: Academic Journals
Citation: Micallef, C., Shoemake, C., & Azzopardi, L. M. (2013). Creating a high-throughput screening database to propose ligands capable of modulating the HIV-1 protease receptor. Journal of AIDS and HIV Research, 5(7), 224-234.
Abstract: This is a report of a de novo design study that aimed to identify novel structures capable of inhibiting the human immune deficiency virus (HIV-1) protease ligand binding pocket (HIV-1 PR_LBP). Baseline information regarding ligand binding modality and affinity was obtained through analysis of the pdb crystallographic depositions describing the HIV-1 PR enzyme complexed with small molecule inhibitors currently available on the Protein Data Bank (PDB). Molecular visualisation and modelling was carried out using SYBYL® 1.1, and in silico predicted ligand binding affinity (LBA) was quantified using XSCORE_V1.3. The de novo design phase of the study was based on the utilisation of the bound coordinates of Lopinavir. This particular HIV-1 protease (HIV-1 PR) inhibitor was selected as a template owing to its superior in vivo activity and unique binding modality. Based on literature derived data, the cyclic urea moiety of Lopinavir was retained as a seed fragment, overlaid onto its counterpart moiety and planted into the HIV-1 PR_LBP with growth being allowed according to defined parameters utilising the genetic algorithm embedded in the GROW module of LIGBUILDER®V1.2. The result was the identification of 200 de novo designed structures with a predicted in silico ligand binding affinity (LBA) (pKd) ranging between 9.63 and 10.00. A smaller cohort (n = 35) was also Lipinski rule of 5 complaint. The implication of this study consequently is that this series of novel structures may be compiled into a library that may be of utility in high throughput screening (HTS) processes and future iterative optimisation.
Appears in Collections:Scholarly Works - FacM&SPha

Items in OAR@UM are protected by copyright, with all rights reserved, unless otherwise indicated.