%0 Journal Article
%T Metal¨Cligand interactions in drug design
%J -
%D 2018
%R https://doi.org/10.1038/s41570-018-0018-6
%X The fast-growing body of experimental data on metalloenzymes and organometallic compounds is fostering the exploitation of metal¨Cligand interactions for the design of new drugs. Atomistic understanding of the metal¨Cligand interactions will help us identify potent metalloenzyme inhibitors and metallodrugs. Static docking calculations have proved effective in identifying hit compounds that target metalloproteins. However, the flexibility, dynamics and electronic structure of metal-centred complexes pose difficult challenges for shaping metal¨Cligand interactions in structure-based drug design. In this respect, once-prohibitive quantum mechanics-based strategies and extensive molecular simulations are rapidly becoming practical approaches for fast-paced drug discovery. These methods account for ligand exchange and structural flexibility at metal-centred complexes and provide good estimates of the thermodynamics and kinetics of metal-aided drug binding. This Perspective examines the successes, limitations and new avenues for modelling metalloenzyme inhibitors and metallodrugs to further explore and expand the unconventional chemical space of these distinctive drugs
%U https://www.nature.com/articles/s41570-018-0018-6