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In this regard, deep neural network algorithms are now deployed which can capture very complex input feature space. However, one fundamental challenge in applying deep learning to structures of binding sites is the input representation and the reference frame. We report here a novel algorithm, Site2Vec, that derives reference frame invariant vector embedding of a protein\u2013ligand binding site. The method is based on pairwise distances between representative points and chemical compositions in terms of constituent amino acids of a site. The vector embedding serves as a locality sensitive hash function for proximity queries and determining similar sites. The method has been the top performer with more than 95% quality scores in extensive benchmarking studies carried over 10 data sets and against 23 other site comparison methods in the field. The algorithm serves for high throughput processing and has been evaluated for stability with respect to reference frame shifts, coordinate perturbations and residue mutations. We also provide the method as a standalone executable and a web service hosted at (http:\/\/services.iittp.ac.in\/bioinfo\/home).<\/jats:p>","DOI":"10.1088\/2632-2153\/abad88","type":"journal-article","created":{"date-parts":[[2020,8,7]],"date-time":"2020-08-07T22:46:08Z","timestamp":1596840368000},"page":"015005","update-policy":"https:\/\/doi.org\/10.1088\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Site2Vec: a reference frame invariant algorithm for vector embedding of protein\u2013ligand binding sites"],"prefix":"10.1088","volume":"2","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4059-6414","authenticated-orcid":false,"given":"Arnab","family":"Bhadra","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9237-5453","authenticated-orcid":false,"given":"Kalidas","family":"Yeturu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"266","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"mlstabad88bib1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1000387","article-title":"Drug discovery using chemical systems biology: identification of the protein\u2013ligand binding network to explain the side effects of cetp inhibitors","volume":"5","author":"Xie","year":"2009","journal-title":"PLoS Comput. 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Published by IOP Publishing Ltd","name":"copyright_information","label":"Copyright Information"},{"value":"2020-05-18","name":"date_received","label":"Date Received","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-08-07","name":"date_accepted","label":"Date Accepted","group":{"name":"publication_dates","label":"Publication dates"}},{"value":"2020-12-01","name":"date_epub","label":"Online publication date","group":{"name":"publication_dates","label":"Publication dates"}}]}}