FINDSITE(X): a structure-based, small molecule virtual screening approach with application to all identified human GPCRs.

Molecular Pharmaceutics
Hongyi Zhou, Jeffrey Skolnick

Abstract

We have developed FINDSITE(X), an extension of FINDSITE, a protein threading based algorithm for the inference of protein binding sites, biochemical function and virtual ligand screening, that removes the limitation that holo protein structures (those containing bound ligands) of a sufficiently large set of distant evolutionarily related proteins to the target be solved; rather, predicted protein structures and experimental ligand binding information are employed. To provide the predicted protein structures, a fast and accurate version of our recently developed TASSER(VMT), TASSER(VMT)-lite, for template-based protein structural modeling applicable up to 1000 residues is developed and tested, with comparable performance to the top CASP9 servers. Then, a hybrid approach that combines structure alignments with an evolutionary similarity score for identifying functional relationships between target and proteins with binding data has been developed. By way of illustration, FINDSITE(X) is applied to 998 identified human G-protein coupled receptors (GPCRs). First, TASSER(VMT)-lite provides updates of all human GPCR structures previously modeled in our lab. We then use these structures and the new function similarity detection algorit...Continue Reading

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Citations

Dec 18, 2012·Journal of Chemical Information and Modeling·Hongyi Zhou, Jeffrey Skolnick
Oct 13, 2015·Journal of Cheminformatics·Janez KoncDušanka Janežič
Mar 27, 2015·Journal of Molecular Recognition : JMR·Elizabeth YurievPaul A Ramsland
Aug 1, 2015·Journal of Chemical Information and Modeling·Ambrish RoyJeffrey Skolnick
Dec 30, 2014·Trends in Pharmacological Sciences·Yu-Chian Chen
Aug 4, 2016·Biogerontology·Terry W SnellJeffrey Skolnick
Aug 11, 2015·Chemical Communications : Chem Comm·Claudio N Cavasotto, Damián Palomba
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Aug 14, 2012·Journal of Applied Toxicology : JAT·Luis G Valerio, Supratim Choudhuri
Apr 22, 2020·Drug Development Research·Kanica Sachdev, Manoj K Gupta
Mar 17, 2021·Journal of Chemical Information and Modeling·Hongyi ZhouJeffrey Skolnick
Jun 14, 2021·The Journal of Biological Chemistry·Robin Pearce, Yang Zhang
Jan 31, 2019·Journal of Chemical Information and Modeling·Thomas LitfinYaoqi Zhou
Oct 3, 2018·Journal of Chemical Information and Modeling·Hongyi ZhouJeffrey Skolnick

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