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The effects of ligand charge, orientation and size on the binding of potential inhibitors for aldehyde dehydrogenase
Magee, Caroline A Peterson, Larryn W Cafiero, Mauricio Selner, Emma F
Magee, Caroline A
Peterson, Larryn W
Cafiero, Mauricio
Selner, Emma F
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2020-05-20
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Abstract
l-DOPA, used as a therapy for patients with Parkinson’s disease, is transformed into needed dopamine in the brain. This dopamine can then be deactivated via metabolism by a series of enzymes, including aldehyde dehydrogenase (ALDH). The targeted inhibition of the ALDH enzyme may help to prolong l-DOPA therapy. A series of potential inhibitors has been studied via ab initio models using a crystal-structure of the ALDH enzyme with an inhibitor bound in its active site (PDB ID: 4WP7). The positions of novel dopaminergic derivatives were optimized in the active site using M062X/6-31G with implicit solvation and relaxed amino-acid side-chains. This work examines different single molecule orientations, as well as double molecule configurations. Various sizes of ligands were also studied. Interaction energies between the ligands and the protein were calculated using M062X with the 6–311 + G* basis set. Some potential inhibitors show promising results such as the LP and CAM series.
Citation
Magee, C.A., Peterson, L.W., Cafiero, M. and Selner, E.F. (2020) The effects of ligand charge, orientation and size on the binding of potential inhibitors for aldehyde dehydrogenase, Computational and Theoretical Chemistry, 1185, 112868. https://doi.org/10.1016/j.comptc.2020.112868
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Journal article
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en
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This is an accepted manuscript of an article published by Elsevier in Computational and Theoretical Chemistry on 20/05/2020, available online: https://doi.org/10.1016/j.comptc.2020.112868
The accepted version of the publication may differ from the final published version.
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2210-271X