Optibrium, a number one developer of software program and AI options for molecular design at the moment introduced the publication of a peer-reviewed research within the Journal of Laptop-Aided Molecular Design, ‘Construction-Based mostly Pose Prediction: Non-cognate Docking Prolonged to Macrocylic Ligands’. The paper demonstrates that Surflex-Dock can precisely predict the binding conformation and orientation (pose) of unknown (non-cognate) ligands, together with macrocycles.
Molecular docking is a comparatively simple course of for re-docking identified (cognate) ligands of proteins, exhibiting very excessive success charges. Nonetheless, in any real-world utility, it’s unknown binding companions which can be underneath investigation, equivalent to predicting the binding mode of a candidate ligand throughout a drug design course of. Predicting binding interactions in these eventualities is known as non-cognate molecular docking, which usually has a a lot decrease success price. Non-cognate docking is especially difficult for macrocyclic compounds given their measurement and adaptability.
Utilizing an information set of ~1000 ligands, the research in contrast totally different molecular docking strategies to foretell the non-cognate binding of non-macrocyclic and macrocyclic ligands. Utilizing the Surflex-Dock methodology, appropriate poses among the many two top-ranked predictions have been recognized 80% of the time, successful price far exceeding these noticed for AutoDock Vina and Gnina, notably for macrocyclic ligands. In actual fact, the non-cognate macrocycle docking efficiency of Optibrium’s methodology rivals different studies of cognate non-macrocycle small molecule docking.
Along with demonstrating the excellent efficiency of Surflex-Dock for advanced docking eventualities, the paper gives a benchmark for the group to find out the success of different strategies on real-world molecular design purposes.
This paper studies, for the primary time, extremely correct outcomes for macrocyclic ligand conformation and orientation prediction which match the accuracy proven for various non-macrocyclic ligands. Crucially, the outcomes characterising Surflex-Dock’s efficiency have been achieved with ensembles of macrocycle-naive protein buildings. Setting a brand new benchmark for non-cognate docking, our analysis underlines how Surflex-Dock is main the sector for chemists creating each macrocyclic and small molecule modalities and validates using Optibrium’s BioPharmics platform for creating macrocyclic therapeutics.”
Ann Cleves, VP of Software Science, BioPharmics Division, Optibrium
Wish to be taught extra about our Surflex-Dock molecular docking methodology?
On 14 November, two of the authors of this paper, Ajay Jain and Ann Cleves, will focus on the most recent developments across the Surflex-Dock methodology in our webinar. They will additionally present a hands-on demonstration of Surflex-Dock in motion addressing quite a lot of docking examples.