Publication detail

In silico investigation of cholesterol-lowering drugs to find potential inhibitors of dehydrosqualene synthase in Staphylococcus aureus

BHOGAL, I. PANKAJ, V. ROY, S. PROVAZNÍK, V.

Original Title

In silico investigation of cholesterol-lowering drugs to find potential inhibitors of dehydrosqualene synthase in Staphylococcus aureus

Type

journal article in Web of Science

Language

English

Original Abstract

Staphylococcus aureus is a lethal pathogen that can cause various bacterial infections. This study targets the CrtM enzyme of S. aureus, which is crucial for synthesizing golden carotenoid pigment: staphyloxanthin, which provides anti-oxidant activity to this bacterium for combating antimicrobial resistance inside the host cell. The present investigation quests for human SQS inhibitors against the CrtM enzyme by employing structure-based drug design approaches including induced fit docking (IFD), molecular dynamic (MD) simulations, and binding free energy calculations. Depending upon the docking scores, two compounds, lapaquistat acetate and squalestatin analog 20, were identified as the lead molecules exhibit higher affinity toward the CrtM enzyme. These docked complexes were further subjected to 100 ns MD simulation and several thermodynamics parameters were analyzed. Further, the binding free energies (ΔG) were calculated for each simulated protein–ligand complex to study the stability of molecular contacts using the MM-GBSA approach. Pre-ADMET analysis was conducted for systematic evaluation of physicochemical and medicinal chemistry properties of these compounds. The above study suggested that lapaquistat acetate and squalestatin analog 20 can be selected as potential lead candidates with promising binding affinity for the S. aureus CrtM enzyme. This study might provide insights into the discovery of potential drug candidates for S. aureus with a high therapeutic index.

Keywords

Anti-virulence, CrtM, docking, MM-GBSA, molecular dynamics, staphyloxanthin, virtual screening

Authors

BHOGAL, I.; PANKAJ, V.; ROY, S.; PROVAZNÍK, V.

Released

17. 1. 2024

Publisher

Springer

ISBN

2190-5738

Periodical

3 Biotech

Year of study

14

Number

2

State

Federal Republic of Germany

Pages count

11

URL

https://link.springer.com/article/10.1007/s13205-023-03862-y

BibTex

@article{BUT185401,
  author="Inderjeet {Bhogal} and Vaishali {Pankaj} and Sudeep {Roy} and Valentine {Provazník}",
  title="In silico investigation of cholesterol-lowering drugs to find potential inhibitors of dehydrosqualene synthase in Staphylococcus aureus",
  journal="3 Biotech",
  year="2024",
  volume="14",
  number="2",
  pages="11",
  doi="10.1007/s13205-023-03862-y",
  issn="2190-5738",
  url="https://link.springer.com/article/10.1007/s13205-023-03862-y"
}