Predicting Blood-Brain Partitioning of Small Molecules Using a Novel Minimalistic Descriptor-Based Approach via the 3D-RISM-KH Molecular Solvation Theory

Abstract

Compartmentalization of drug molecules between plasma and brain is important for desired activities. The difficulty in obtaining the blood-brain permeability of drug (like) substances experimentally resulted in the development of several theoretical quantitative structure-activity relationships toward predicting the capability of a given substrate to pass across a tight junction, known as the blood-brain barrier, both qualitatively and quantitatively. Here, we report a novel method based on the molecular solvation theory for predicting blood-brain barrier permeability coefficients of molecules of diverse structures using a minimum set of descriptors derived from solvation energetics. Our finding points to the importance of solvation free energy based descriptors in modeling blood-brain barrier permeability quantitatively.