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

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216305%3A26220%2F24%3APU149582" target="_blank" >RIV/00216305:26220/24:PU149582 - isvavai.cz</a>

Result on the web

<a href="https://link.springer.com/article/10.1007/s13205-023-03862-y" target="_blank" >https://link.springer.com/article/10.1007/s13205-023-03862-y</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s13205-023-03862-y" target="_blank" >10.1007/s13205-023-03862-y</a>

Result language

angličtina

Original language name

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

Original language description

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.

Czech name

—

Czech description

—

Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

—

OECD FORD branch

30401 - Health-related biotechnology

Project

—

Continuities

S - Specificky vyzkum na vysokych skolach

Publication year

2024

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

3 Biotech

ISSN

2190-572X

e-ISSN

2190-5738

Volume of the periodical

14

Issue of the periodical within the volume

2

Country of publishing house

DE - GERMANY

Number of pages

11

Pages from-to

„“-„“

UT code for WoS article

001144214900004

EID of the result in the Scopus database

—