Title

COARSE GRAINED PARAMETERIZATION OF THE GRAM-NEGATIVE BACTERIAL MEMBRANE

Date of Award

5-2015

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Shikha Nangia

Keywords

coarse grain, gram negative bacteria, molecular dynamics simulations

Subject Categories

Biological Engineering | Biology | Biomedical Engineering and Bioengineering | Chemical Engineering | Chemistry

Abstract

The outermost membrane of gram-negative bacteria is a lipopolysaccharide (LPS) rich bilayer assembly that acts as the first line of defense for bacterial cells in adverse physical and chemical environments. Besides the LPS, the outer membrane has radially extending O-antigen polysaccharide chains and β-barrel membrane proteins that make the bacterial membrane physiologically unique compared to the phospholipid cell membranes. To study the molecular complexity and dynamics of the LPS rich membrane, we have developed coarse grained parameter set for the outer membrane compatible with the Martini force field. The coarse grained model was benchmarked against available experimental and atomistic simulations data for properties such as membrane thickness, density profiles of the residues, area per lipid, gel to liquid-crystalline phase transition temperatures, order parameters, and radial distribution functions. More than 17 membrane compositions were studied with a combined simulation time of over 100 microseconds. A comparison of simulated structural and dynamical properties with corresponding experimental data shows that the developed parameter set reproduces the overall physiology of LPS membranes. The coarse grained model of the outer membrane makes long timescale simulations feasible, which can be instrumental in designing effective antibiotics with enhanced outer membrane permeation properties.

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