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<p>Recent studies have highlighted the crucial application of marine natural products (MNPs) as potential antibiotics against <i>Pseudomonas aeruginosa</i>, a pathogen liable to show antimicrobial resistance and controlled through quorum sensing. MNPs by nature possess great potential for the discovery and development of novel antibiotics to overcome drug resistance. This work utilized diverse MNPs from the marine natural product database (MNPD) and seaweed databases as the source to screen for MNPs that have the potential as important lead molecules to inhibit the quorum sensing activity of LasR from <i>P. aeruginosa</i>. Initially, a structure-based virtual screening (SBVS) research was conducted to identify MNPs that can inhibit the catalytic function of LasR. Thereafter, the molecular stability of their interactions was investigated to identify stable binding orientations. The virtual screening assisted study pinpointed three MNPs, MNPD9262, MNPD5388, and SWMD-BS008 as promising alternative molecules, given their acceptable pharmacokinetic properties and lack of toxicity, as predicted by QikProp, pkCSM and ProTox-II. The obtained docking scores ranged from − 9.10 to − 12.89&#xa0;kcal/mol and MMGBSA binding scores ranged from − 45.59 to − 69.09&#xa0;kcal/mol, which were comparatively higher than the control molecule (autoinducer TP1). The favourable docked poses were further analyzed for structural and binding stability using all-atom molecular dynamics simulation (MDS), followed by essential dynamics (ED) analysis, including principal component (PC) based free energy landscape (FEL) analyses. The estimated binding free energy calculations using both MM-GBSA and MM-PBSA revealed the strong and stable binding interactions between the selected MNPs and the LasR binding pocket.</p> Graphical Abstract <p></p>

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Computational Screening of Marine Natural Products against Pseudomonas Aeruginosa LasR: an Integrated Approach Combining Virtual Screening, Quantum Mechanics, and Structural Dynamics for Quorum Sensing Inhibition

  • 期刊论文

  • 发表日期：

    2026年2月27日

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  • Santhiya Panchalingam,
  • Nirmal Bharathi Mayil,
  • Mohd Sajid Ali,
  • Hamad A. Al-Lohedan,
  • Rajalakshmi Kumar,
  • Ravi Deva Asirvatham,
  • Manikandan Jayaraman

摘要

Recent studies have highlighted the crucial application of marine natural products (MNPs) as potential antibiotics against Pseudomonas aeruginosa, a pathogen liable to show antimicrobial resistance and controlled through quorum sensing. MNPs by nature possess great potential for the discovery and development of novel antibiotics to overcome drug resistance. This work utilized diverse MNPs from the marine natural product database (MNPD) and seaweed databases as the source to screen for MNPs that have the potential as important lead molecules to inhibit the quorum sensing activity of LasR from P. aeruginosa. Initially, a structure-based virtual screening (SBVS) research was conducted to identify MNPs that can inhibit the catalytic function of LasR. Thereafter, the molecular stability of their interactions was investigated to identify stable binding orientations. The virtual screening assisted study pinpointed three MNPs, MNPD9262, MNPD5388, and SWMD-BS008 as promising alternative molecules, given their acceptable pharmacokinetic properties and lack of toxicity, as predicted by QikProp, pkCSM and ProTox-II. The obtained docking scores ranged from − 9.10 to − 12.89 kcal/mol and MMGBSA binding scores ranged from − 45.59 to − 69.09 kcal/mol, which were comparatively higher than the control molecule (autoinducer TP1). The favourable docked poses were further analyzed for structural and binding stability using all-atom molecular dynamics simulation (MDS), followed by essential dynamics (ED) analysis, including principal component (PC) based free energy landscape (FEL) analyses. The estimated binding free energy calculations using both MM-GBSA and MM-PBSA revealed the strong and stable binding interactions between the selected MNPs and the LasR binding pocket.

Graphical Abstract