Unveiling quorum sensing mechanisms: Computational docking and dynamics of bacterial receptors and ligands

IF 4 2区化学 Q2 CHEMISTRY, PHYSICAL Journal of Molecular Structure Pub Date : 2024-11-13 DOI:10.1016/j.molstruc.2024.140730

Sana Malik , Faiza Akram , Muhammad Ali , Mohsin Javed , Rana Muhammad Mateen , Ammar Zidan , Ali Bahadur , Shahid Iqbal , Sajid Mahmood , Abd-ElAziem Farouk , Salman Aloufi

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Abstract

The bacterial cell-to-cell communication mechanism known as quorum sensing (QS) uses chemical cues called autoinducers (AIs) to control several processes, including pathogenicity, antibiotic resistance, and biofilm formation. This study investigates the QS receptor-ligand interactions and QS compatibility within and between bacterial species using computational molecular docking. Receptor proteins including LuxS, LuxP, AgrC, LuxN, SdiA, LasR, esaR, YenR, LamC, PlcR, and TraR were docked with their respective AIs (AHL, AI-1, AI-2, AIP1, LamD, PapR7) in both biofilm and non-biofilm producing bacteria. Our findings indicate that QS receptors exhibit high affinity for their cognate ligands, with binding affinities ≥ -4.5 Kcal/mol. Additionally, Zinc Pharmar-derived similar chemical structures demonstrated binding affinities ≥ -5.3 Kcal/mol. Density Functional Theory (DFT) analysis revealed AI-2 as the most reactive autoinducer. Molecular Dynamics (MD) simulations confirmed the stability of LasR-AHL and LuxP-AI-2 complexes. These insights pave the way for further in vitro and in vivo investigations of QS mechanisms.

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揭示法定人数感应机制：细菌受体和配体的计算对接与动力学

被称为 "法定量感应"（QS）的细菌细胞间通讯机制利用被称为 "自动诱导剂"（AIs）的化学线索来控制多个过程，包括致病性、抗生素耐药性和生物膜的形成。本研究利用计算分子对接研究了细菌物种内部和之间的 QS 受体-配体相互作用和 QS 兼容性。在生物膜和非生物膜产生细菌中，包括 LuxS、LuxP、AgrC、LuxN、SdiA、LasR、esaR、YenR、LamC、PlcR 和 TraR 在内的受体蛋白与各自的 AI（AHL、AI-1、AI-2、AIP1、LamD、PapR7）进行了对接。我们的研究结果表明，QS 受体与其同源配体具有很高的亲和力，结合亲和力≥ -4.5 Kcal/mol。此外，Zinc Pharmar 衍生的类似化学结构也显示出结合亲和力≥ -5.3 Kcal/mol。密度泛函理论（DFT）分析表明，AI-2 是活性最高的自体诱导剂。分子动力学（MD）模拟证实了 LasR-AHL 和 LuxP-AI-2 复合物的稳定性。这些见解为进一步研究 QS 的体外和体内机制铺平了道路。

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来源期刊

Journal of Molecular Structure 化学-物理化学

CiteScore

7.10

自引率

15.80%

发文量

2384

审稿时长

45 days

期刊介绍： The Journal of Molecular Structure is dedicated to the publication of full-length articles and review papers, providing important new structural information on all types of chemical species including: • Stable and unstable molecules in all types of environments (vapour, molecular beam, liquid, solution, liquid crystal, solid state, matrix-isolated, surface-absorbed etc.) • Chemical intermediates • Molecules in excited states • Biological molecules • Polymers. The methods used may include any combination of spectroscopic and non-spectroscopic techniques, for example: • Infrared spectroscopy (mid, far, near) • Raman spectroscopy and non-linear Raman methods (CARS, etc.) • Electronic absorption spectroscopy • Optical rotatory dispersion and circular dichroism • Fluorescence and phosphorescence techniques • Electron spectroscopies (PES, XPS), EXAFS, etc. • Microwave spectroscopy • Electron diffraction • NMR and ESR spectroscopies • Mössbauer spectroscopy • X-ray crystallography • Charge Density Analyses • Computational Studies (supplementing experimental methods) We encourage publications combining theoretical and experimental approaches. The structural insights gained by the studies should be correlated with the properties, activity and/ or reactivity of the molecule under investigation and the relevance of this molecule and its implications should be discussed.