title: PockDrug-Server: a new web server for predicting pocket druggability on holo and apo proteins.
abstract: Predicting protein pocket's ability to bind drug-like molecules with high affinity, i.e. druggability, is of major interest in the target identification phase of drug discovery. Therefore, pocket druggability investigations represent a key step of compound clinical progression projects. Currently computational druggability prediction models are attached to one unique pocket estimation method despite pocket estimation uncertainties. In this paper, we propose 'PockDrug-Server' to predict pocket druggability, efficient on both (i) estimated pockets guided by the ligand proximity (extracted by proximity to a ligand from a holo protein structure) and (ii) estimated pockets based solely on protein structure information (based on amino atoms that form the surface of potential binding cavities). PockDrug-Server provides consistent druggability results using different pocket estimation methods. It is robust with respect to pocket boundary and estimation uncertainties, thus efficient using apo pockets that are challenging to estimate. It clearly distinguishes druggable from less druggable pockets using different estimation methods and outperformed recent druggability models for apo pockets. It can be carried out from one or a set of apo/holo proteins using different pocket estimation methods proposed by our web server or from any pocket previously estimated by the user. PockDrug-Server is publicly available at: http://pockdrug.rpbs.univ-paris-diderot.fr.
authors.affiliation: INSERM, UMRS-973, MTi, Université Paris Diderot, 35 Rue Hélène Brion, 75205 Paris Cedex 13, case courier 7113, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMRS-973, MTi, Paris, France.
authors.forename: Hiba Abi
authors.initials: HA
authors.lastname: Hussein
authors.affiliation: INSERM, UMRS-973, MTi, Université Paris Diderot, 35 Rue Hélène Brion, 75205 Paris Cedex 13, case courier 7113, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMRS-973, MTi, Paris, France Division of Pharmaceutical Chemistry, Faculty of pharmacy, University of Helsinki, Viikinkaari 9 (P.O. Box 56) FI-00014, Finland.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Borrel
authors.affiliation: INSERM, UMRS-973, MTi, Université Paris Diderot, 35 Rue Hélène Brion, 75205 Paris Cedex 13, case courier 7113, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMRS-973, MTi, Paris, France.
authors.forename: Colette
authors.initials: C
authors.lastname: Geneix
authors.affiliation: INSERM, UMRS-973, MTi, Université Paris Diderot, 35 Rue Hélène Brion, 75205 Paris Cedex 13, case courier 7113, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMRS-973, MTi, Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Petitjean
authors.affiliation: INSERM, UMRS-973, MTi, Université Paris Diderot, 35 Rue Hélène Brion, 75205 Paris Cedex 13, case courier 7113, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMRS-973, MTi, Paris, France.
authors.forename: Leslie
authors.initials: L
authors.lastname: Regad
authors.affiliation: INSERM, UMRS-973, MTi, Université Paris Diderot, 35 Rue Hélène Brion, 75205 Paris Cedex 13, case courier 7113, Paris, France Université Paris Diderot, Sorbonne Paris Cité, UMRS-973, MTi, Paris, France anne-claude.camproux@univ-paris-diderot.fr.
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Camproux
mesh_terms: D001059:Apoproteins / Q000737:chemistry*; D001665:Binding Sites; D055808:Drug Discovery / Q000379:methods*; D020407:Internet; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011485:Protein Binding; D011487:Protein Conformation; D011506:Proteins / Q000737:chemistry; D012984:Software
chemical_list: D001059:Apoproteins; D004364:Pharmaceutical Preparations; D011506:Proteins