| Abstract
| - Molecular descriptors calculated by the VolSurf program have been extensively used to modelpharmacokinetic properties, e.g., passive permeability through the gastrointestinal tract orthrough the blood−brain barrier. These descriptors quantify steric, hydrophobic, and hydrogenbond interactions between model compounds and different environments. Since these interactions are the same as those involved in the ligand−receptor binding, VolSurf descriptors couldpotentially be relevant in modeling this process as well. We obtained a significant model (r2 =0.85, q2 = 0.75) using VolSurf descriptors derived from the ligand, the protein, and the ligand−protein complex for a diverse set of 38 structures previously used in the VALIDATE (ref )training set. Furthermore, a statistically significant model (r2 = 0.94, q2 = 0.89) was obtainedusing the same type of descriptors for a homogeneous set of glycogen phosphorylase inhibitors(ref ). Using the VolSurf computational framework, both ligand−receptor binding and theligand's pharmacokinetic behavior can be modeled simultaneously during the preclinical aspectsof drug discovery.
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