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Epik: a software program for pK a prediction and protonation state generation for drug-like molecules
- Source :
- Journal of Computer-Aided Molecular Design. 21:681-691
- Publication Year :
- 2007
- Publisher :
- Springer Science and Business Media LLC, 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.
- Subjects :
- Models, Molecular
Cell Membrane Permeability
Molecular model
Membrane permeability
Ligand
Chemistry
Quantitative Structure-Activity Relationship
Protonation
Affinities
Tautomer
Computer Science Applications
Lewis structure
symbols.namesake
Pharmaceutical Preparations
Computational chemistry
Drug Discovery
symbols
Molecule
Protons
Physical and Theoretical Chemistry
Software
Subjects
Details
- ISSN :
- 15734951 and 0920654X
- Volume :
- 21
- Database :
- OpenAIRE
- Journal :
- Journal of Computer-Aided Molecular Design
- Accession number :
- edsair.doi.dedup.....192e9ab08090a0e6a3744d582acdadce