Apprehending outer membrane models of Gram-negative bacteria at different atomistic resolutions for in silico antibiotic developments

¹ Mathematics Department, School of Computer Science, Bina Nusantara University, 11480 Jakarta, Indonesia
² Bioinformatics and Data Science Research Center, Bina Nusantara University, 11480 Jakarta, Indonesia
³ Biotechnology Department, Faculty of Engineering, Bina Nusantara University, 11480 Jakarta, Indonesia
⁴ BINUS Graduate Program‑Master of Computer Science Program, Bina Nusantara University, 11480 Jakarta, Indonesia

^* Corresponding author: alam.ahmad@binus.ac.id

Abstract

Antimicrobial resistance (AMR) poses one of the major risks for the current and future global public health. Gram-negative pathogens with their unique outer membrane are regularly put on the WHO critical priority list to tackle the AMR challenges. The rapid and collaborative developments of high-efficacy antibiotics against these bacteria are thus highly anticipated. For example, outer membrane proteins of Gram-negative bacteria are currently promising targets for novel antimicrobial drugs. Advances in current computing technology may aid in designing a well-targeted experiment study and understanding the molecular mechanism of the drugs. In this study, we demonstrate how to build a model and a simulation setup of ß-barrel assembly machinery A protein embedded in an outer membrane of Escherichia Coli using two different model resolutions: atomistic and coarse-grained force fields. We employed atomistic parameters from the CHARMM force field and novel lipopolysaccharides parameters in the Martini 3 force field. The built models were shown to be stable as the energy minimization procedure can achieve convergence within an appropriate potential energy range. The modeling pipeline demonstrated in this preliminary study is expected to facilitate the in-silico development of antibiotics for combating different Gram-negative pathogens.