Calculation of Molecular Physicochemical Properties

LogP (octanol/water partition coefficient)

LogP is calculated by the methodology developed by Molinspiration as a sum of fragment-based contributions and correction factors. Method is very robust and is able to process practically all organic, and most organometallic molecules.

Molecular Polar Surface Area TPSA

is calculated based on the methodology published by Ertl et al. [1] as a sum of fragment contributions. O- and N- centered polar fragments are considered. PSA has been shown to be a very good descriptor characterizing drug absorption, including intestinal absorption, bioavailability, Caco-2 permeability and blood-brain barrier penetration.

Molecular Volume

Method for calculation of molecule volume developed at Molinspiration is based on group contributions. These have been obtained by fitting sum of fragment contributions to "real" 3D volume for a training set of about twelve thousand, mostly drug-like molecules. 3D molecular geometries for a training set were fully optimized by the semiempirical AM1 method.

"Rule of 5" Properties

is set of simple molecular descriptors used by Lipinski in formulating his "Rule of 5" [2]. The rule states, that most "drug-like" molecules have logP <= 5, molecular weight <= 500, number of hydrogen bond acceptors <= 10, and number of hydrogen bond donors <= 5. Molecules violating more than one of these rules may have problems with bioavailability. The rule is called "Rule of 5", because the border values are 5, 500, 2*5, and 5.

Number of Rotatable Bonds - nrotb

This simple topological parameter is a measure of molecular flexibility. It has been shown to be a very good descriptor of oral bioavailability of drugs [3]. Rotatable bond is defined as any single non-ring bond, bounded to nonterminal heavy (i.e., non-hydrogen) atom. Amide C-N bonds are not considered because of their high rotational energy barrier.

Molinspiration Batch Property Calculation Toolkit mib

Molinspiration offers a molecular processing and property calculation toolkit written in Java. The toolkit may be used in a batch mode to process large number of molecules (processing speed is about 10,000 molecules/minute), or accessed through web interface directly on your intranet. Calculated molecular descriptors may be used for property based virtual screening of large collections of molecules to discard structures with not drug-like properties and to pick potential drug candidates.
For more information about the Toolkit or to arrange a free evaluation at your site, contact please info [at] molinspiration.com.

References

• P. Ertl, B. Rohde, P. Selzer, Fast calculation of molecular polar surface area as a sum of fragment-based contributions and its application to the prediction of drug transport properties. J.Med.Chem. 43, 3714-3717 (2000).
• C.A. Lipinski, F. Lombardo, B.W. Dominy, P.J. Feeney, Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv.Drug.Delivery Rev. 23, 4-25 (1997).
• D.F. Veber, S.R. Johnson, H.-Y. Cheng, B.R. Smith, K.W. Ward, K.D. Kopple, Molecular properties that influence the oral bioavailability of drug candidates. J.Med.Chem. 45, 2615-2623 (2002).

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