Inhibitor design for <scp>3‐hydroxy‐3‐methyl‐glutaryl‐CoA</scp> reductase enzyme; molecular docking and determination of molecular and electronic properties of ligands by density functional theory method

Abstract Designing new inhibitors having less side effects is a need which also could reduce cholesterol levels. To fulfill this aim, we have carried out a molecular docking study toward 3‐hydroxy‐3‐methyl‐glutaryl‐CoA (HMG‐CoA) reductase. A set of designed structural derivatives of statin drugs, eight ligands which are used as HIV‐1 integrase inhibitor candidates, a set of terpenoids, and ligands downloaded from Zinc15 database were docked to HMG‐CoA reductase enzyme which contains atorvastatin in crystal structure. The analysis of docking studies revealed that statin derivative ligands are more appropriate for inhibition of HMG‐CoA reductase. To define the contribution of the molecular properties to the binding of ligands to enzyme structure; the highest occupied molecular orbitals‐lowest unoccupied molecular orbitals, hardness, electronegativity, and chemical potential properties of ligands have best score in their sets calculated by quantum mechanical tools.

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