Computational Screening of FDA‐Approved PPIs and PCABs against LasR Protein: Insights into Quorum Sensing Inhibition
Abstract
Addressing bacterial infections caused by multi‐drug resistant bacteria is a global priority. One promising approach to overcoming the challenge of multi‐drug resistance involves inhibiting bacterial quorum sensing mechanisms. Quorum sensing (QS) inhibitors are emerging as potential alternatives to traditional antibiotics. In this study, FDA approved proton pump inhibitors (PPIs) and potassium‐competitive acid blockers (PCABs) were screened using in silico methods to evaluate their effectiveness in targeting the LasR protein which has a role in the QS mechanism of
Pseudomonas aeruginosa
. Tegoprazan and Lansoprazole exhibit strong binding affinity for the LasR protein, with binding free energies of −9.23 and −9.09 kcal/mol, respectively. Molecular dynamic (MD) simulations (100 ns) of the docked complexes revealed that Tegoprazan and Lansoprazole remained stably bound within the LasR protein's binding pocket most of the time of simulation. Throughout the simulation, the backbone of both complexes showed minor variations in RMSD and
R
g
. The free energy landscape of the LasR‐Tegoprazan and LasR‐Lansoprazole complexes indicated strong stability. Both complexes exhibited excellent Molecular Mechanic/Poisson‐Boltzmann surface area (MM/PBSA) based binding free energies: −101.443 ± 12.845 kJ/mol for LasR‐Tegoprazan and −81.867 ± 14.633 kJ/mol for LasR‐Lansoprazole. In this study, we also investigate the DFT‐based electronic characteristics of these drugs in different solvents.
Read the paper
Related studies
- Prevalence and Characteristics of Autism Spectrum Disorder Among Children Aged 8 Years — Autism and Developmental Disabilities Monitoring Network, 11 Sites, United States, 2018
- Improving sleep quality leads to better mental health: A meta-analysis of randomised controlled trials
- Community transmission and viral load kinetics of the SARS-CoV-2 delta (B.1.617.2) variant in vaccinated and unvaccinated individuals in the UK: a prospective, longitudinal, cohort study
- Occupation and risk of severe COVID-19: prospective cohort study of 120,075 UK Biobank participants
- Clinical presentation and virological assessment of confirmed human monkeypox virus cases in Spain: a prospective observational cohort study
- Comparison of the characteristics, morbidity, and mortality of COVID-19 and seasonal influenza: a nationwide, population-based retrospective cohort study
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.