Reviewed by Susan Boyd, CompChem Solutions
Molecular Discovery was established 25 years ago to develop and distribute the original GRID software.1 GRID was used in the design of the anti-flu drug Relenza, so their software is not to be sneezed at! GRID characterises the electronic properties of input molecules, and Molecular Discovery have subsequently developed an array of software products based on the GRID force field. Two of these products are MoKa and MetaSite.
MoKa is a pKa calculator, which employs an algorithm using GRID-based descriptors to compute pKa to within 0.4 log units for most structures.2 Values for the octanol-water distribution coefficient, LogD, are also computed. Additionally, MoKa also advises the user of the most stable tautomeric form of the structure, which greatly improves the consistency and accuracy of physico-chemical property predictions.
The user interface is quite intuitive, and presents an evaluation of the likely accuracy of the prediction, together with interactive graphs showing how the ionised species distribution varies with pH. Cut-and-paste from ISIS/Draw is supported, although a variety of file formats can be imported, and results can be output as .png image files.
MetaSite predicts phase I cytochrome P450 (CYP450) metabolic transformations, identifying both likely sites of metabolism and the probable metabolites.3 It has been developed using experimental data accessed through the CYP Consortium Initiative, which includes four of the top six big pharmaceutical companies. Although the CYP protein library provided with the program is quite comprehensive, users can input their own CYP structures to the software to develop additional models. A useful feature is the flagging of functionalities which help to direct the molecule into the CYP cavity to enable metabolism. Exporting of results in html format is a real bonus to aid distribution of the derived data.
More information on MoKa and MetaSite can be obtained.
, 2172 (DOI: 10.1021/ci700018y)