MOLECULAR DYNAMICS SIMULATION OF MYCOBACTERIUM TUBERCULOSIS MEMBRANES: COMPARATIVE ANALYSIS OF PIM2 AND DPPC LIPID MODELS

Yago Mendes Paes; Karina Machado; Adriano Werhli

Paper Title

Authors

Yago Mendes Paes
Karina Machado
Adriano Werhli

Modality

Poster

Subject area

Proteins and Proteomics

Publishing Date

21/11/2024

Country of Publishing

Brazil | Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeeting-2024/832855-molecular-dynamics-simulation-of-mycobacterium-tuberculosis-membranes--comparative-analysis-of-pim2-and-dppc-lipi

ISBN

978-65-272-0843-3

Keywords

Membrane biophysics,Lipid bilayers,Protein-lipid interactions,Structural dynamics

Summary

Tuberculosis (TB) is a bacterial infection caused mainly by the organism Mycobacterium tuberculosis (Mtb), and it is the second most prevalent infectious illness worldwide, particularly in developing countries. Furthermore, the COVID-19 pandemic has set back years of progress in reducing the number of cases and deaths caused by TB, with a decrease in the reported number of people diagnosed and reduced access to TB treatment. The emergence of drug-resistant strains of Mtb is one of the major issues regarding the treatment of this disease. In addition to acquired resistance, Mtb exhibits high degrees of intrinsic resistance due to its active efflux system, which can transport a variety of substrates from the interior to the exterior of the cell, allied to its unusual thick lipid-rich and impermeable cell wall that restricts treatment options. From its efflux system, the Rv1258c efflux pump (TAP), is a transmembrane protein associated with resistance to isoniazid and rifampicin, and mutations to its gene can confer drug resistance to pyrazinamide, streptomycin, and isoniazid. The cell wall of Mtb consists mostly of lipids from the phosphatidyl-myo-inositol mannosides (PIMs) family, phosphatidyl-myo-inositol dimannosides (PIM2) being the most abundant, which are confirmed to have immunomodulatory properties that contribute to the pathogenesis of TB. Understanding the composition and behavior of biological membranes is crucial for comprehending their physiological roles, conformations, and morphologies, shedding light on their physicochemical characteristics and how they interact with key proteins like the TAP efflux pump through molecular dynamics simulations, which can help exploring these membranes in detail.Molecular Dynamics (MD) is one of the employed methods to understand the behavior of cell membranes. MD is an in-silico approach that allows complete control of the biological system properties and has been used to provide information on both spatial organization and temporal dynamics. Studies on Mtb membranes often involve various lipid compositions, such as dipalmitoylphosphatidylcholine (DPPC), phosphatidylethanolamine (POPE), and dioleoylphosphatidylcholine (DOPC) in order to explore the membrane behavior. There are no membrane models with such uncommon and specific lipid composition as the ones contained in the PIM family. In the present work, we propose to perform all atom MD simulations with GROMACS 2023.2 using a PIM2 membrane model of Mtb and a DPPC membrane, containing the TAP protein, comparing the structural behavior of these membranes in order to analyze the potential of PIM2 as a membrane model and to understand how the lipids will be affected with the presence of the TAP protein. The systems were simulated individually, and each consisted of a bilayer membrane comprising 128 PIM2 lipids or DPPC lipids perpendicular to the Z-axis, with the TAP protein centered in the middle of the bilayer. Preliminary findings suggest that the PIM2 membrane model behaves similarly to DPPC, presenting more stable compositions when TAP protein was inserted, considering it had lower values of root mean square deviation (RMSD) of its structure and lower lateral diffusion values of the PIM2 phosphorus atoms. TAP also exhibited lower RMSD values on its protein helix while incorporated within the PIM2 bilayer.

Title of the Event: 20º Congresso Brasileiro de Bioinformática: X-Meeting 2024
City of the Event: Salvador
Title of the Proceedings of the event: X-Meeting presentations
Name of the Publisher: Even3
Means of Dissemination: Meio Digital

How to cite

PAES, Yago Mendes; MACHADO, Karina; WERHLI, Adriano. MOLECULAR DYNAMICS SIMULATION OF MYCOBACTERIUM TUBERCULOSIS MEMBRANES: COMPARATIVE ANALYSIS OF PIM2 AND DPPC LIPID MODELS.. In: X-Meeting presentations. Anais...Salvador(BA) Hotel Deville Prime, 2024. Available in: https//www.even3.com.br/anais/xmeeting-2024/832855-MOLECULAR-DYNAMICS-SIMULATION-OF-MYCOBACTERIUM-TUBERCULOSIS-MEMBRANES--COMPARATIVE-ANALYSIS-OF-PIM2-AND-DPPC-LIPI. Access in: 01/05/2025