Large-scale prediction of binding affinity in protein-small ligand complexes: the PRODIGY-LIG web server

SUMMARY Recently we published PROtein binDIng enerGY (PRODIGY), a web-server for the prediction of binding affinity in protein-protein complexes. By using a combination of simple structural properties, such as the residue-contacts made at the interface, PRODIGY has demonstrated a top performance compared with other state-of-the-art predictors in the literature. Here we present an extension of it, named PRODIGY-LIG, aimed at the prediction of affinity in protein-small ligand complexes. The predictive method, properly readapted for small ligand by making use of atomic instead of residue contacts, has been successfully applied for the blind prediction of 102 protein-ligand complexes during the D3R Grand Challenge 2. PRODIGY-LIG has the advantage of being simple, generic and applicable to any kind of protein-ligand complex. It provides an automatic, fast and user-friendly tool ensuring broad accessibility. AVAILABILITY AND IMPLEMENTATION PRODIGY-LIG is freely available without registration requirements at http://milou.science.uu.nl/services/PRODIGY-LIG.

[1]  Gianni De Fabritiis,et al.  KDEEP: Protein-Ligand Absolute Binding Affinity Prediction via 3D-Convolutional Neural Networks , 2018, J. Chem. Inf. Model..

[2]  Anna Vangone,et al.  Contacts-based prediction of binding affinity in protein–protein complexes , 2015, eLife.

[3]  Z. Weng,et al.  A structure‐based benchmark for protein–protein binding affinity , 2011, Protein science : a publication of the Protein Society.

[4]  Tania Pencheva,et al.  AMMOS2: a web server for protein–ligand–water complexes refinement via molecular mechanics , 2017, Nucleic Acids Res..

[5]  Anna Vangone,et al.  PRODIGY: A Contact-based Predictor of Binding Affinity in Protein-protein Complexes. , 2017, Bio-protocol.

[6]  Irina S. Moreira,et al.  Performance of HADDOCK and a simple contact-based protein–ligand binding affinity predictor in the D3R Grand Challenge 2 , 2017, Journal of Computer-Aided Molecular Design.

[7]  Philippe Roche,et al.  2P2Idb v2: update of a structural database dedicated to orthosteric modulation of protein–protein interactions , 2016, Database J. Biol. Databases Curation.

[8]  Shuai Liu,et al.  D3R Grand Challenge 2: blind prediction of protein–ligand poses, affinity rankings, and relative binding free energies , 2017, Journal of Computer-Aided Molecular Design.

[9]  Pierre Tufféry,et al.  MTiOpenScreen: a web server for structure-based virtual screening , 2015, Nucleic Acids Res..

[10]  Michal Brylinski,et al.  Nonlinear Scoring Functions for Similarity-Based Ligand Docking and Binding Affinity Prediction , 2013, J. Chem. Inf. Model..

[11]  Tarun Jain,et al.  An all atom energy based computational protocol for predicting binding affinities of protein–ligand complexes , 2005, FEBS letters.

[12]  Raphael A. G. Chaleil,et al.  Updates to the Integrated Protein-Protein Interaction Benchmarks: Docking Benchmark Version 5 and Affinity Benchmark Version 2. , 2015, Journal of molecular biology.

[13]  Jung-Hsin Lin,et al.  idTarget: a web server for identifying protein targets of small chemical molecules with robust scoring functions and a divide-and-conquer docking approach , 2012, Nucleic Acids Res..

[14]  Alexandre M. J. J. Bonvin,et al.  PRODIGY: a web server for predicting the binding affinity of protein-protein complexes , 2016, Bioinform..

[15]  Douglas E. V. Pires,et al.  CSM-lig: a web server for assessing and comparing protein–small molecule affinities , 2016, Nucleic Acids Res..

[16]  Zhihai Liu,et al.  Forging the Basis for Developing Protein-Ligand Interaction Scoring Functions. , 2017, Accounts of chemical research.

[17]  G. Folkers,et al.  Proteins feel more than they see: fine-tuning of binding affinity by properties of the non-interacting surface. , 2014, Journal of molecular biology.

[18]  Alexandre M J J Bonvin,et al.  Modeling protein-protein complexes using the HADDOCK webserver "modeling protein complexes with HADDOCK". , 2014, Methods in molecular biology.