The Hydrogen-Bond: computational approaches and applications to drug design.

Abstract

This mini-review situates the hydrogen bond within the broader landscape of intermolecular recognition forces relevant to molecular biology and pharmacology. Various computational strategies for quantifying hydrogen-bonding capacity are surveyed, encompassing quantum mechanical approaches, molecular mechanics, and fragment-based algorithms derived from experimental data. A notable recent development is the formulation of molecular hydrogen-bonding potentials (MHBPs) as specialized molecular interaction fields (MIFs). The utility of MHBPs in linking molecular properties to pharmacokinetic parameters is illustrated through two case studies: oral drug absorption and blood-brain barrier permeation. The review underscores the growing role of these computational tools in rational drug design.

Mechanism

Molecular hydrogen-bonding potentials (MHBPs), a class of molecular interaction fields, are used to quantify the hydrogen-bonding capacity of compounds and correlate these properties with pharmacokinetic parameters such as oral absorption and blood-brain barrier permeation.