AutoGridFR: Improvements on AutoDock Affinity Maps and Associated Software Tools

Abstract

Precomputed affinity maps are used by AutoDock to efficiently describe rigid biomolecules called receptors in automated docking. These maps greatly speed up the docking process and allow users to experiment with the forcefield. Here, we present AutoGridFR (AGFR): a software tool facilitating the calculation of these maps. We describe a new version of the AutoSite algorithm that improves the description of binding pockets automatically detected on receptors, and an algorithm for adding affinity gradients which help search methods optimize solution using fewer evaluations of the scoring functions. AGFR supports the calculation of maps for various advanced docking techniques such as covalent docking, hydrated docking, and docking with flexible receptor sidechains. Maps are stored in a single file along with metadata supporting data provenance, reproducibility, and facilitating their management. Finally, maps can be calculated from the command line or through a modern graphical user interface which also supports their visualization. © 2019 Wiley Periodicals, Inc.

Predicting binding sites from unbound versus bound protein structures

“…AutoSite 14 , 33 is an energy-based method which uses AutoDock 68 affinity maps computed with AutoGrid4 69 for three generic atom-type grids to identify binding sites 14 . These maps are regularly spaced grids, and the three AutoDock generic atom types are hydrophobic (carbon, C), hydrogen-bond acceptor (oxygen, OA), and hydrogen-bond donor (hydrogen, HD).…”

“…The resulting points are then clustered to find putative binding sites. Recent improvements help to merge closely spaced clusters into larger pockets 33 .…”

“…These methods utilize probe molecules and chemical moieties to generate potentials for locating binding sites. Some examples of energy-based methods include: AutoSite 14 , 33 , PocketFinder 6 , SiteHound 34 , Q-SiteFinder 35 , and FTSite 36 .…”

TheAutoDocksuite at 30

“…AutoDockFR (ADFR, "Flexible Receptor") is a parallel development effort that addresses the limitation of a rigid receptor, 20,21 building on the earlier FLIPDock F I G U R E 3 Many simplifications are imposed to improve speed of docking. (a) Interaction energies for probe atoms are calculated volumetrically.…”

“…AutoDockFR (ADFR, “Flexible Receptor”) is a parallel development effort that addresses the limitation of a rigid receptor, 20,21 building on the earlier FLIPDock program 22,23 . AD4 and ADVina include the ability to model user‐defined flexible side chains explicitly, but ADFR creates a more general representation of the receptor, allowing definition of sidechains, loops, and domains undergoing motions during conformational searches 24 .…”