Sébastien Rey, Mehrva Rabii, Giulia Caron, Giuseppe Ermondi, Patrick Gaillard,Alessandra Pagliara, Pierre-Alain Carrupt and Bernard Testa
Institute of Medicinal Chemistry, University of Lausanne, BEP, CH-1015 Lausanne.

Hydrogen bonds are major forces of recognition in biochemistry and molecular pharmacology, and as such they are an essential component of intermolecular interactions, being to a significant extent responsible for the 3D-structure of biomacromolecules and for the exquisite specificity of ligand-receptor interactions.

A new method is presented which takes into account the recognition capacity of H-bonds, namely Molecular Hydrogen Bonds Potentials (MHBPs). This method is based on a stepwise procedure similar to the one used successfully to generate the Molecular Lipophilicity Potential (MLP).

An atomic H-bond donor fragmental value is associated with each hydrogen atom in a polar moiety. Similarly, an atomic H-bond acceptor fragmental value is associated to polar atoms.

The initial donor and acceptor atomic fragmental values were developed from an extensive database of solvatochromic parameters ? and ?? The MHBPs on each point of the space were calculated as the product of the fragmental values on each polar moiety (lone pairs on acceptor atoms, and H atoms in polar moiety) by a function which takes into account the distance and the angle between this point and the polar moiety.

These new potentials were used as an additional field in CoMFA studies or in score similarity functions. They were also tested with success to predict oral drug absorption. Available examples demonstrate that the MHBPs offer an interesting computational tool in drug design.