The inhibition of LpxC, an enzyme responsible for the first committed step of the biosynthesis of Lipid A, is critical in developing novel antibacterial treatments for Gram-negative bacteria. The inhibition of LpxC would prevent the production of Lipid A, which would then corrupt the outer membrane of Gram-negative bacteria. Using the crystal structure with a natural substrate bound in the active site (PDB ID 2IER), novel ligands have been designed and optimized in the active site. Ligands have been designed and studied without the nucleoside in order to determine the importance of zinc binding and the hydrophobic moiety. These structures were optimized using M06L and the 6-31G basis set. Interaction energies for ligand-amino acid interactions have been calculated using M06L with the 6-311-G* basis set. The computational analysis of these non-nucleoside containing potential inhibitors will be discussed.

Computational analysis of non-nucleoside containing molecules as potential inhibitors of LpxC

255th National Meeting (2018)

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