Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0021051 (immunodeficiency)
 71,517 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Structure- and ligand-based virtual-screening methods (docking, 2D- and 3D-similarity searching) were analysed for their effectiveness in virtual screening against four different targets: angiotensin-converting enzyme (ACE), cyclooxygenase 2 (COX-2), thrombin and human immunodeficiency virus 1 (HIV-1) protease. The relative performance of the tools was compared by examining their ability to recognise known active compounds from a set of actives and nonactives. Furthermore, we investigated whether the application of different virtual-screening methods in parallel provides complementary or redundant hit lists. Docking was performed with GOLD, Glide, FlexX and Surflex. The obtained docking poses were rescored by using nine different scoring functions in addition to the scoring functions implemented as objective functions in the docking algorithms. Ligand-based virtual screening was done with ROCS (3D-similarity searching), Feature Trees and Scitegic Functional Fingerprints (2D-similarity searching). The results show that structure- and ligand-based virtual-screening methods provide comparable enrichments in detecting active compounds. Interestingly, the hit lists that are obtained from different virtual-screening methods are generally highly complementary. These results suggest that a parallel application of different structure- and ligand-based virtual-screening methods increases the chance of identifying more (and more diverse) active compounds from a virtual-screening campaign.
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PMID:Comparison of structure- and ligand-based virtual screening protocols considering hit list complementarity and enrichment factors. 1990 72

Attachment of envelope glycoprotein gp120 to the host cell receptor CD4 is the first step during the human immunodeficiency virus-1 (HIV-1) entry into the host cells that makes it a promising target for drug design. To elucidate the crucial three dimensional (3D) structural features of reported HIV-1 gp120 CD4 binding inhibitors, 3D pharmacophores were generated and receptor based approach was employed to quantify these structural features. A four-partial least square factor model with good statistics and predictive ability was generated for the dataset of 100 molecules. To further ascertain the structural requirement for gp120-CD4 binding inhibition, molecular interaction studies of inhibitors with gp120 was carried out by performing molecular docking using Glide 5.6. Based on these studies, structural requirements were drawn and new molecules were designed accordingly to yield new sulphonamides derivatives. A water based green synthetic approach was adopted to obtain these compounds which were evaluated for their HIV-1 gp120 CD4 binding inhibition. The newly synthesized compounds exhibited remarkable activity (10-fold increase) when compared with the standard BMS 806. Further the stability of newly synthesized derivatives with HIV-1 gp120 was also investigated through molecular dynamics simulation studies. This provides a proof of concept for molecular modeling based design of new inhibitors for inhibition of HIV-1 gp120 CD4 interaction.
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PMID:Computational design, synthesis and evaluation of new sulphonamide derivatives targeting HIV-1 gp120. 3179 86