Use of MIF-based VolSurf Descriptors in Physicochemical and Pharmacokinetic Studies

Use of MIF-based VolSurf Descriptors in Physicochemical and Pharmacokinetic Studies 

Raimund Mannhold, Ciuliano Berellini, Emanuele Carosati, and Paolo Benedetti 

This is the framework where computational chemistry could play an important role in the prediction of these properties in order to obtain more efficient and faster drug discovery cycles. To obtain useful descriptors for ADME properties is not an easy task. A large number of descriptors have been developed [4], all of which have major limitations in terms of relevance, interpretability or speed of calculation. 

Alternatively, calculated molecular properties from 3D molecular fields of interaction energies represent a valuable approach to correlate 3 D molecular structures with physicochemical and pharmacodynamic properties. In contrast, their use in correlations with pharmacokinetic properties is still poorly explored and exploited. The rather new VolSurf approach [5-7] is able to compress the relevant information present in 3D maps into a few descriptors characterized by the simplicity of 

In the updated version, presented here, VolSurf descriptors are enlarged from 72 to 94. The new descriptors include elongation, diffusivity, logP, and the so-called best volumes. Definition of the original VolSurf descriptors is given in [5-7] and in Table 8.1 the novel descriptors are additionally defined in detail below. 

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I 8 Use of MIF-based VolSurf Descriptors in Physicochemical and Pharmacokinetic Studies TableS.I Detailed definition ofVolSurfdescriptors. 

Mannhold, R., Berellini, G., Carosati, E., Benedetti, P. Use of MIF-based VolSurf descriptors in physicochemical and pharmacokinetic studies. In Molecular Interaction Fields (Cruciani, G., Ed.), In Methods and Principles in Medicinal Chemistry (Mannhold, R., Kubinyi, H., Folkers, G., Eds), Vol. 27, Wiley-VCH Weinheim, 2006, pp. 173-196. 

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