Deep understanding of lipid bilayers in three phases at the molecular level could potentially lead us to design a novel artificial membrane. Molecular modeling of bacterial membranes is important as they are cheap and an environmentally friendly candidate to produce fuels. Molecular investigation of transmembrane proteins is crucial as mutations in them were observed in multiple diseases including cancer.

The inner membrane of Escherichia coli (E. coli) was modeled to include lipid diversity and demonstrate that this is needed to properly probe the interaction of lipids and transmembrane proteins. Molecular dynamics (MD) simulations were used with the all-atom CHARMM36 (C36) force field. Lipid diversity affects the properties of the E. coli inner membrane and indicated the importance of including lipids with different head groups and acyl chains. The effect of the growth stage of the E.coli colony significantly influenced thicknesses and bulk properties of the membrane.

Phase transitions of fully saturated lipid bilayers, 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-phosphocholine (DPPC) and their mixtures were probed for the first time using MD simulations. The phase transitions from fluid (Lα) phase to ripple (Pβ) phase and to the gel (Lβ) phase were obtained within temperature range in good agreement with experimental phase transition temperature. DMPC and DPPC bilayers in Lβ phase resulted in fatty acid chains tilted relative to bilayer normal and with average tilt angle in agreement with experiment. MD simulations revealed molecular-level structural details of the pure DMPC bilayer in Pβ phase at a temperature to compare to experimental X-Ray diffraction measurements. The structure of the major and minor arm is in agreement with experiment when enough lipids are used to model this phase.

The final two topics involved collaborations with experimental labs to provide insight into experimental observables. First, MD simulations successfully showed that improved tolerance and production of biorenewables of a metabolically engineered E.coli strain is the result of increased bilayer thickness. Secondly, MD simulations of the homodimerization of plexin A3 were used to probe the association of the transmembrane (TM) and juxtamembrane (JM) domains of this important cell-signaling membrane protein. These simulations indicated multiple dimerization conformations, and suggested importance of extracellular domain residues on strong TM interactions.