title: CSM-lig: a web server for assessing and comparing protein-small molecule affinities.
abstract: Determining the affinity of a ligand for a given protein is a crucial component of drug development and understanding their biological effects. Predicting binding affinities is a challenging and difficult task, and despite being regarded as poorly predictive, scoring functions play an important role in the analysis of molecular docking results. Here, we present CSM-Lig (http://structure.bioc.cam.ac.uk/csm_lig), a web server tailored to predict the binding affinity of a protein-small molecule complex, encompassing both protein and small-molecule complementarity in terms of shape and chemistry via graph-based structural signatures. CSM-Lig was trained and evaluated on different releases of the PDBbind databases, achieving a correlation of up to 0.86 on 10-fold cross validation and 0.80 in blind tests, performing as well as or better than other widely used methods. The web server allows users to rapidly and automatically predict binding affinities of collections of structures and assess the interactions made. We believe CSM-lig would be an invaluable tool for helping assess docking poses, the effects of multiple mutations, including insertions, deletions and alternative splicing events, in protein-small molecule affinity, unraveling important aspects that drive protein-compound recognition.
authors.affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, 30190-002, Brazil douglas.pires@cpqrr.fiocruz.br.
authors.forename: Douglas E V
authors.initials: DE
authors.lastname: Pires
authors.affiliation: Centro de Pesquisas René Rachou, Fundação Oswaldo Cruz, Belo Horizonte, 30190-002, Brazil Department of Biochemistry, University of Cambridge, Cambridge, CB2 1GA, UK Department of Biochemistry, University of Melbourne, Victoria 3010, Australia dascher@svi.edu.au.
authors.forename: David B
authors.initials: DB
authors.lastname: Ascher
mesh_terms: D030562:Databases, Protein; D066264:Datasets as Topic; D020407:Internet; D008024:Ligands; D062105:Molecular Docking Simulation; D009154:Mutation; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry* / Q000235:genetics; D015203:Reproducibility of Results; D054852:Small Molecule Libraries / Q000737:chemistry* / Q000494:pharmacology; D012984:Software; D013379:Substrate Specificity; D014584:User-Computer Interface
chemical_list: D008024:Ligands; D011506:Proteins; D054852:Small Molecule Libraries