Peón López, AntonioCoderch, ClaireGago, FedericoGonzález Bello, Concepción2018-07-022018-07-022013-04-26Peón, A., Coderch, C., Gago, F., & González-Bello, C. (2013). Comparative Binding Energy (COMBINE) Analysis for Understanding the Binding Determinants of Type II Dehydroquinase Inhibitors. Chemmedchem, 8(5), 740-747. doi: 10.1002/cmdc.2013000131860-7179http://hdl.handle.net/10347/16925This is the peer-reviewed version of the following article: Peón, A., Coderch, C., Gago, F., & González-Bello, C. (2013). Comparative Binding Energy (COMBINE) Analysis for Understanding the Binding Determinants of Type II Dehydroquinase Inhibitors. Chemmedchem, 8(5), 740-747, which has been published in final form at https://doi.org/10.1002/cmdc.201300013. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingHerein we report comparative binding energy (COMBINE) analyses to derive quantitative structure–activity relationship (QSAR) models that help rationalize the determinants of binding affinity for inhibitors of type II dehydroquinase (DHQ2), the third enzyme of the shikimic acid pathway. Independent COMBINE models were derived for Helicobacter pylori and Mycobacterium tuberculosis DHQ2, which is an essential enzyme in both these pathogenic bacteria that has no counterpart in human cells. These studies quantify the importance of the hydrogen bonding interactions between the ligands and the water molecule involved in the DHQ2 reaction mechanism. They also highlight important differences in the ligand interactions with the interface pocket close to the active site that could provide guides for future inhibitor designeng© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This article may be used for non-commercial purposes in accordance with Wiley-VCH Terms and Conditions for Self-ArchivingAntibioticsBinding interactionsCompetitive inhibitorsDehydroquinasesStructure–activity relationshipsjournal article10.1002/cmdc.2013000131860-7187open access