ADME VolSurf

VOLSURF A Tool for Drug ADME-properties Prediction... 

In the following section, the calculation of the VolSurf parameters from GRID interaction energies will be explained and the physico-chemical relevance of these novel descriptors demonstrated by correlation with measured absorption/ distribution/metabolism/elimination (ADME) properties. The applications will be shown by correlating 3D molecular structures with Caco-2 cell permeabilities, thermodynamic solubilities and metabolic stabilities. Special emphasis will be placed on interpretation of the models by multivariate statistics, because a rational design to improve molecular properties is critically dependent on an understanding of how molecular features influence physico-chemical and ADME properties. 

I. Zamora, R. Mannhold. VOLSURF A Tool for Drug ADME-properties Prediction, in Drug Bioavailability. Estimation of Solubility, Permeability and Absorption, Methods and Principles in Medicinal Chemistry, vol. 18, (eds. H. van de Waterbeemd, H. Lennernas, P. Artursson), Wiley-VCH, Weinheim, pp. 406 19, 2003. 

In addition to the VolSurf treatment of the GRID fields, the information from the MIF can also be transformed to obtain a pharmacophoric type of representation, which is useful in the modeling of metabolic stability, cytochrome inhibition or even the direct study of the ADME related proteins (Fig. 10.3). The Almond software [17] transforms the MIF into a distance-based representation of the molecule interaction. These parameters describe the geometry of the interaction and QSAR models can be derived where the interaction with a protein is essential. Detailed information on these descriptors is presented elsewhere in this book. 

Cruciani, G. Meniconi, M. Carosati, E. Zamora, I. Mannhold R. VOLSURF A Tool for Drug ADME-Properties Prediction, in Drug Bioavailability, Water-beemd, H. Lennemas, H. Artursson,... 

VolSurfwas initially validated on oral absorption [16, 17] and blood-brain-barrier permeation [18] models (see belovi ). VolSurf has continued to be developed to improve in silico predictions for ADME properties, although its use has also been extended to receptor-based evaluation of binding affinity [19, 20], While other soft-ivare tools for ADME modeling are available (see, e.g., [21]), the MIF-based collection of sofhvare and models available from Molecular Discovery (MD) is both extensive and ivell validated by the private sector. Three programs from MD, VolSurf, MetaSite and Almond, are particularly suited for rapid evaluation of large compound sets [22] in connection ivith ADME/Tox related properties ... 

The GRID force field represents the basis for several software packages specifically developed for application to pharmacodynamic aspects of drug research, including the programs ALMOND, Pathfinder, and FLAP or, in the ADME field, the programs VolSurf and MetaSite. 

Cruciani, G., Meniconi, M., Carosati, E., Zamora, 1. and Mannhold, R. (2003) VolSurf a tool for drug ADME-properties prediction, in Drug Bioavailability, Vol. 18, Wiley-VCH Verlag GmbH, Weinheim, Germany, pp. 406-419. 

VolSurf—calculate ADME properties and create predictive ADME models Available at ... 

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