MOLECULAR DYNAMICS SIMULATIONS OF MYCOBACTERIUM TUBERCULOSIS PIM2 MEMBRANE WITH BENZOHYDROXAMATES

Yago Mendes Paes; Lucas Thadeu Felipe Kokuszi; Vania Rodrigues de Lima; Adriano Werhli; Karina Machado

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Paper Title

MOLECULAR DYNAMICS SIMULATIONS OF MYCOBACTERIUM TUBERCULOSIS PIM2 MEMBRANE WITH BENZOHYDROXAMATES

Authors

Yago Mendes Paes
Lucas Thadeu Felipe Kokuszi
Vania Rodrigues de Lima
Adriano Werhli
Karina Machado

Modality

Xpress presentation

Subject area

Structural Bioinformatics

Publishing Date

26/04/2022

Country of Publishing

Brasil

Language of Publishing

Inglês

Paper Page

https://www.even3.com.br/anais/xmeetingxp2021/420629-molecular-dynamics-simulations-of-mycobacterium-tuberculosis-pim2-membrane-with-benzohydroxamates

ISBN

978-65-5941-645-5

Keywords

Molecular dynamics simulations, Mycobacterium tuberculosis, membrane

Summary

Tuberculosis (TB) is a bacterial infection caused by Mycobacterium tuberculosis (Mtb), which infects approximately one-third of the global population. TB treatment remains challenging due to drug resistance as well as the thick lipid-rich cell wall of Mtb. Therefore, it is necessary the development of new drugs and effective strategies against this pathogen. In this context, salts derived from hydroxamic acids such as benzohydroxamate (BH) are considered promising compounds for treating TB. However, the comprehension of the dynamic interaction between structural components of the Mtb cell wall with these active substances is necessary. An important tool for this purpose is Molecular Dynamics (MD) Simulations. Phosphatidyl-myo-inositol mannosides (PIMs) are an essential component of the cell envelope and the most predominant lipid in the inner membrane of Mtb. In a previous work, we have modeled PIM2 Mtb membrane. In the present work, we propose to perform MD simulations of BH with the PIM2 model of Mtb to evaluate their interactions. We perform the MD simulations using GROMACS 2021. The molecules of BH were designed with the software Avogadro and minimized with semi-empirical methods using MOPAC 2016. In the next step, we submitted the minimized configurations of BH molecule to the Automated Topology Builder website to create the topology and force fields parameters used in GROMACS 2021. The simulated system comprises the membrane, which is composed of 128 PIM2 lipids divided into two layers perpendicular to the Z axis, with two water boxes closer to the lipid-heads of the constructed bilayer. 12 molecules of BH were placed in these water boxes. The entire system has a neutral charge and goes through equilibration processes of temperature, pressure, and energy minimization. After that, the production phase by MD will be performed and the results analyzed. The expected results are changes in the deuterium parameters, area per lipid headgroup, and lateral diffusion of the lipids, mainly caused by BH related to changes in the molecular packaging of the Mtb membrane, making it more susceptible to the actions of the active substances.

Title of the Event: X-Meeting XPerience 2021
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 et al.. MOLECULAR DYNAMICS SIMULATIONS OF MYCOBACTERIUM TUBERCULOSIS PIM2 MEMBRANE WITH BENZOHYDROXAMATES.. In: X-Meeting presentations. Anais...São Paulo(SP) AB3C, 2021. Available in: https//www.even3.com.br/anais/xmeetingxp2021/420629-MOLECULAR-DYNAMICS-SIMULATIONS-OF-MYCOBACTERIUM-TUBERCULOSIS-PIM2-MEMBRANE-WITH-BENZOHYDROXAMATES. Access in: 01/05/2025