Mycobacterium, a genus of Gram-positive bacteria, are responsible for illnesses such as tuberculosis that remain as global health concerns. A unique characteristic of mycobacteria is their highly complex, multilayered mycobacterial outer and inner membranes that are believed to play a key role in immune system evasion and resistance to small molecule permeation. The slow growth of many mycobacteria species and their toxicity make it difficult to experimentally derive structural characteristics of these membranes. Molecular dynamics simulations can provide an alternative method to study membrane properties, thereby bypassing some of these issues. However, the presence of many unique lipids and glycoconjugates within the mycobacterial membranes poses a significant barrier to the creation of simulation systems. To facilitate the simulation of membranes containing mycobacterial lipids, we have introduced the mycobacterial lipid modeler (MBLM) in CHARMM-GUI. MBLM allows for the generation of a set of predefined mycobacterial lipids including phosphatidyl-myo-inositol mannosides (PIMs), lipomannan (LM), lipoarabinomannan (LAM), mycolates, phthiocerol dimycocerosates (PDIMs), and trehalose-containing glycolipids. To accommodate for a large diversity of mycobacterial lipids, MBLM also supports multiple customization options, such as creating unique mannan cores for LM and LAM, multiple options for lipid tails, and initial folded states of mycolates among others. To further simplify the creation of membrane systems containing mycobacterial lipids, MBLM has been integrated into membrane builder, making it possible to build an entire mycomembrane/protein complex in a simple workflow, and thus increasing the complexity and realism of buildable systems. Overall, MBLM and its integration into membrane builder will significantly reduce the work necessary to build and simulate membranes with mycobacterial lipids, allowing for further research into unique structures and properties of the mycobacterial inner and outer membranes.
Rygh et al. (Sun,) studied this question.