NDLI: Accurate calculation of the absolute free energy of binding for drug molecules† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc02678d

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Accurate calculation of the absolute free energy of binding for drug molecules† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5sc02678d

Content Provider	Semantic Scholar
Author	Aldeghi, Matteo Heifetz, Alexander Bodkin, Michael J. Knapp, Stefan Biggin, Philip C.
Copyright Year	2016
Abstract	Accurate prediction of binding affinities has been a central goal of computational chemistry for decades, yet remains elusive. Despite good progress, the required accuracy for use in a drug-discovery context has not been consistently achieved for drug-like molecules. Here, we perform absolute free energy calculations based on a thermodynamic cycle for a set of diverse inhibitors binding to bromodomain-containing protein 4 (BRD4) and demonstrate that a mean absolute error of 0.6 kcal mol-1 can be achieved. We also show a similar level of accuracy (1.0 kcal mol-1) can be achieved in pseudo prospective approach. Bromodomains are epigenetic mark readers that recognize acetylation motifs and regulate gene transcription, and are currently being investigated as therapeutic targets for cancer and inflammation. The unprecedented accuracy offers the exciting prospect that the binding free energy of drug-like compounds can be predicted for pharmacologically relevant targets.
Starting Page	207
Ending Page	218
Page Count	12
File Format	PDF HTM / HTML
DOI	10.1039/C5SC02678D
Alternate Webpage(s)	https://pubs.rsc.org/en/content/articlepdf/2016/sc/c5sc02678d?page=search
Alternate Webpage(s)	http://www.rsc.org/suppdata/c5/sc/c5sc02678d/c5sc02678d1.pdf
Alternate Webpage(s)	https://dasher.wustl.edu/chem430/readings/chemsci-7-207-16.pdf
Alternate Webpage(s)	https://pubs.rsc.org/en/content/articlepdf/2016/sc/c5sc02678d
Alternate Webpage(s)	http://pubs.rsc.org/en/content/articlepdf/2016/SC/C5SC02678D
PubMed reference number	26798447
Alternate Webpage(s)	https://doi.org/10.1039/C5SC02678D
Journal	Medline
Volume Number	7
Journal	Chemical science
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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