CavityPlus: a web server for protein cavity detection with pharmacophore modelling, allosteric site identification and covalent ligand binding ability prediction

Abstract

CavityPlus is a web server that offers protein cavity detection and various functional analyses. Using protein three-dimensional structural information as the input, CavityPlus applies CAVITY to detect potential binding sites on the surface of a given protein structure and rank them based on ligandability and druggability scores. These potential binding sites can be further analysed using three submodules, CavPharmer, CorrSite, and CovCys. CavPharmer uses a receptor-based pharmacophore modelling program, Pocket, to automatically extract pharmacophore features within cavities. CorrSite identifies potential allosteric ligand-binding sites based on motion correlation analyses between cavities. CovCys automatically detects druggable cysteine residues, which is especially useful to identify novel binding sites for designing covalent allosteric ligands. Overall, CavityPlus provides an integrated platform for analysing comprehensive properties of protein binding cavities. Such analyses are useful for many aspects of drug design and discovery, including target selection and identification, virtual screening, de novo drug design, and allosteric and covalent-binding drug design. The CavityPlus web server is freely available at http://repharma.pku.edu.cn/cavityplus or http://www.pkumdl.cn/cavityplus.

Glycine-induced formation and druggability score prediction of protein surface pockets

“…Fpocket webserver 26 and PLIC 27 are based on Fpocket. CavityPlus 28 and iDrug 29 are based on Cavity, which is mainly focused on predicting sites for covalent ligand binding. DoGSiteScorer 30 and PockDrug webserver 31 are the web interfaces of DoGSite and PockDrug, respectively.…”

Curating the gnomAD database: Report of novel variants in the globin‐coding genes and bioinformatics analysis

“…">To account for the amount and type of amino acid interactions involved in the interfaces between α/β‐globins, α‐globin and AHSP, along with the contacts with the heme and the allosteric modulator 2,3‐DPG, RING (Martin et al, ), and LPC/CSU softwares (Sobolev, Sorokine, Prilusky, Abola, & Edelman, ) were employed. O 2 gate access involved residues were analyzed in different conformations, considering the available data (Boechi et al, ; Bringas, Petruk, Estrin, Capece, & Martí, ), and pockets and cavities estimation was performed using FPocket and CavityPlus programs (Le Guilloux, Schmidtke, & Tuffery, ; Xu et al, ). Missense variants were also analyzed with the sequence‐based predictors PROVEAN (http://provean.jcvi.org/index.php; Choi & Chan, ), SIFT (http://siftdna.org/www/Extended_SIFT_chr_coords_submit.html; Sim et al, ), Panther (http://www.pantherdb.org/tools/csnpScore.do; Mi, Muruganujan, & Thomas, ), SNAP2 (https://open.predictprotein.org/; Bromberg & Rost, ), and with the sequence‐ and structure‐based PolyPhen‐2 (HumVar trained model) (http://genetics.bwh.harvard.edu/pph2/; Adzhubei et al, ). …”

“…O 2 gate access involved residues were analyzed in different conformations, considering the available data (Boechi et al, ; Bringas, Petruk, Estrin, Capece, & Martí, ), and pockets and cavities estimation was performed using FPocket and CavityPlus programs (Le Guilloux, Schmidtke, & Tuffery, ; Xu et al, ).…”

LigBuilder V3: A Multi-Target de novo Drug Design Approach

“…The crystal structures of PR and RT used in this study are downloaded from the RCSB Protein Data Bank (Berman et al, 2003) (PDB code: 3A2O, Hidaka et al, 2009, and4G1Q, Kuroda et al, 2013, respectively), and both structures are complexes with potent inhibitors solved at high resolution (0.88 and 1.51 Å, respectively). The inhibitor binding sites of PR and RT were defined by binding site detection program Cavity (Yuan et al, 2013;Zhang et al, 2015;Xu et al, 2018), which provides the detailed definition for boundary of "design space." The drug-like and privileged building blocks used in this study were inherited from LigBuilder V2.…”