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bioRxiv · 10.1101/2023.07.04.547717

Molecular and Quantum Mechanical Studies of Interaction Between Tetrahydrocurcumin Derivative and PCSK9 Protein to Provide a Basis for an Oral Pill to Remove Bad Cholesterol

Vaithyanathan, P.
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Abstract

The interaction between Proprotein convertase subtilisin/kexin type 9 (PCSK9) and low-density lipoprotein receptors responsible for causing atherosclerosis. According to estimates, it causes 60% of fatalities worldwide and is the covert precursor to clinical myocardial infarction (MI), stroke, and CVD. Designing tiny compounds that inhibit PCSK9 from interacting with LDL receptors is the need of the hour. Through bioinformatics-based studies, this study seeks to assess the interactions between a derivative of tetrahydrocurcumin and PCSK9 Protein and compare them to interactions with the literature based studies of standard Atorvastatin. Additionally, comparison research was carried out to examine how the new compound interacts in the active and allosteric regions of PCSK9. The above-mentioned compound, a derivative of Tetrahydrocurcumin, was adjusted and optimized to the level of local minimum energy using the RCSBs downloaded PDB file 7S5H. By Desmond MD simulation studies, the stability of the non-bonded interactions of the complexes was examined. An affinity of -9.493 kcal/mol for the active site and -8.148 kcal/mol for the allosteric site was observed by docking studies in comparison with the standard molecule, atorvastatin. Also, the MMGBSA value of -50.7142 kcal/mol indicates the Tetrahydrocurcumin derivative binds well compare to the standard, atorvastatin. The Tetrahydro curcumin derivative molecule was able to orient into the active region with the help of Asp238, Thr377, and Ser381 amino acids. In comparison to atorvastatin, the binding affinity was raised by seven H-bonds with six amino acids and one {pi} interaction of Arg295 amino acids of the allosteric site. The Tetrahydro curcumin molecules nonbonded interaction was found to be stable for 100 ns by MD simulation tests. This demonstrates that the Tetrahydrocurcumin derivative molecule will prove to be an effective substrate to modify PCSK9 protein behavior.

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Vaithyanathan, P.. 2023-07-05. Molecular and Quantum Mechanical Studies of Interaction Between Tetrahydrocurcumin Derivative and PCSK9 Protein to Provide a Basis for an Oral Pill to Remove Bad Cholesterol. https://doi.org/10.1101/2023.07.04.547717

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