%0 Journal Article %1 Bowman2011DynamicPharmacophore %A Bowman, Anna L. %A Makriyannis, Alexandros %D 2011 %J Journal of Chemical Information and Modeling %K MD drug-design dynamic-pharmacophore pharmacophore %N 12 %P 3247-3253 %R 10.1021/ci200371z %T Approximating Protein Flexibility through Dynamic Pharmacophore Models: Application to Fatty Acid Amide Hydrolase (FAAH) %U http://dx.doi.org/10.1021/ci200371z %V 51 %X A structure-based drug discovery method is described that incorporates target flexibility through the use of an ensemble of protein conformations. The approach was applied to fatty acid amide hydrolase (FAAH), a key deactivating enzyme in the endocannabinoid system. The resultant dynamic pharmacophore models are rapidly able to identify known FAAH inhibitors over drug-like decoys. Different sources of FAAH conformational ensembles were explored, with both snapshots from molecular dynamics simulations and a group of X-ray structures performing well. Results were compared to those from docking and pharmacophore models generated from a single X-ray structure. Increasing conformational sampling consistently improved the pharmacophore models, emphasizing the importance of incorporating target flexibility in structure-based drug design.

@article{Bowman2011DynamicPharmacophore, abstract = { A structure-based drug discovery method is described that incorporates target flexibility through the use of an ensemble of protein conformations. The approach was applied to fatty acid amide hydrolase (FAAH), a key deactivating enzyme in the endocannabinoid system. The resultant dynamic pharmacophore models are rapidly able to identify known FAAH inhibitors over drug-like decoys. Different sources of FAAH conformational ensembles were explored, with both snapshots from molecular dynamics simulations and a group of X-ray structures performing well. Results were compared to those from docking and pharmacophore models generated from a single X-ray structure. Increasing conformational sampling consistently improved the pharmacophore models, emphasizing the importance of incorporating target flexibility in structure-based drug design. }, added-at = {2017-03-09T20:36:36.000+0100}, author = {Bowman, Anna L. and Makriyannis, Alexandros}, biburl = {https://www.bibsonomy.org/bibtex/2b3b79ef434d7f73a373f0f7f7e6444c1/salotz}, description = {Approximating Protein Flexibility through Dynamic Pharmacophore Models: Application to Fatty Acid Amide Hydrolase (FAAH) - Journal of Chemical Information and Modeling (ACS Publications)}, doi = {10.1021/ci200371z}, eprint = {http://dx.doi.org/10.1021/ci200371z}, interhash = {5110bcb18f7e9e09f9dbb606ae5a4ec3}, intrahash = {b3b79ef434d7f73a373f0f7f7e6444c1}, journal = {Journal of Chemical Information and Modeling}, keywords = {MD drug-design dynamic-pharmacophore pharmacophore}, note = {PMID: 22098169}, number = 12, pages = {3247-3253}, timestamp = {2017-03-09T20:36:36.000+0100}, title = {Approximating Protein Flexibility through Dynamic Pharmacophore Models: Application to Fatty Acid Amide Hydrolase (FAAH)}, url = {http://dx.doi.org/10.1021/ci200371z}, volume = 51, year = 2011 }