NDLI: Epik: a software program for pK$_{ a }$ prediction and protonation state generation for drug-like molecules

Content Provider	Springer Nature Link
Author	Shelley, John C. Cholleti, Anuradha Frye, Leah L. Greenwood, Jeremy R. Timlin, Mathew R. Uchimaya, Makoto
Copyright Year	2007
Abstract	Epik is a computer program for predicting pK$_{a}$ values for drug-like molecules. Epik can use this capability in combination with technology for tautomerization to adjust the protonation state of small drug-like molecules to automatically generate one or more of the most probable forms for use in further molecular modeling studies. Many medicinal chemicals can exchange protons with their environment, resulting in various ionization and tautomeric states, collectively known as protonation states. The protonation state of a drug can affect its solubility and membrane permeability. In modeling, the protonation state of a ligand will also affect which conformations are predicted for the molecule, as well as predictions for binding modes and ligand affinities based upon protein–ligand interactions. Despite the importance of the protonation state, many databases of candidate molecules used in drug development do not store reliable information on the most probable protonation states. Epik is sufficiently rapid and accurate to process large databases of drug-like molecules to provide this information. Several new technologies are employed. Extensions to the well-established Hammett and Taft approaches are used for pK$_{a}$ prediction, namely, mesomer standardization, charge cancellation, and charge spreading to make the predicted results reflect the nature of the molecule itself rather just for the particular Lewis structure used on input. In addition, a new iterative technology for generating, ranking and culling the generated protonation states is employed.
Starting Page	681
Ending Page	691
Page Count	11
File Format	PDF
ISSN	0920654X
Journal	Journal of Computer-Aided Molecular Design
Volume Number	21
Issue Number	12
e-ISSN	15734951
Language	English
Publisher	Springer Netherlands
Publisher Date	2007-09-27
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Hammett and Taft (HT) equations Ionization Mesomers pK$_{ a }$ Protonation state Tautomerization Tautomers Animal Anatomy / Morphology / Histology Computer Applications in Chemistry Physical Chemistry
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Physical and Theoretical Chemistry Computer Science Applications

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