3D-Garden: a system for modelling protein–protein complexes based on conformational refinement of ensembles generated with the marching cubes algorithm

Motivation: Reliable structural modelling of protein–protein complexes has widespread application, from drug design to advancing our knowledge of protein interactions and function. This work addresses three important issues in protein–protein docking: implementing backbone flexibility, incorporating prior indications from experiment and bioinformatics, and providing public access via a server. 3D-Garden (Global And Restrained Docking Exploration Nexus), our benchmarked and server-ready flexible docking system, allows sophisticated programming of surface patches by the user via a facet representation of the interactors’ molecular surfaces (generated with the marching cubes algorithm). Flexibility is implemented as a weighted exhaustive conformer search for each clashing pair of molecular branches in a set of 5000 models filtered from around ∼340 000 initially. Results: In a non-global assessment, carried out strictly according to the protocols for number of models considered and model quality of the Critical Assessment of Protein Interactions (CAPRI) experiment, over the widely-used Benchmark 2.0 of 84 complexes, 3D-Garden identifies a set of ten models containing an acceptable or better model in 29/45 test cases, including one with large conformational change. In 19/45 cases an acceptable or better model is ranked first or second out of 340 000 candidates. Availability: http://www.sbg.bio.ic.ac.uk/3dgarden (server) Contact: v.lesk@ic.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.