A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared

Andrew G. Leach, Lise-Lotte Olsson, Daniel J. Warner

Research output: Contribution to journalArticlepeer-review

Abstract

Two series of compounds that inhibit dimerisation of iNOS have been reported in the literature and studied crystallographically. We have applied a range of docking techniques to these compounds and shown that the geometry of the complexes can be reproduced well but that even within a series of related compounds the docking scores do not rank compounds well. Quantum mechanical studies using a model system for the protein and a range of density functionals are able to reproduce the geometry of the complexes and the corresponding affinities. The combination of docking to generate geometries and quantum mechanical calculations to predict complexation energies is a powerful one for rationalising observed changes and designing improved compounds.
Original languageEnglish
Pages (from-to)180-186
Number of pages7
JournalMedChemComm
Volume4
Issue number1
DOIs
Publication statusPublished - Jan 2013

Fingerprint

Dive into the research topics of 'A monomeric form of iNOS can rationalise observed SAR for inhibitors of dimerisation: quantum mechanics and docking compared'. Together they form a unique fingerprint.

Cite this