This proposal outlines the development and application of new modeling and simulation capabilities for the study of the outer membrane proteins of Pseudomonas aeruginosa and Escherichia coil in realistic, atomicdetail models of the lipopolysaccharide (LPS) membrane. Simulations of lipid bilayers membranes have contributed significantly to our understanding of their energetics and dynamics, as well as the function and dynamics of embedded proteins. However, because of the complexity of LPS membranes, this is not the case for the outer membranes and outer membrane proteins of Gram-negative bacteria. The goal of this work is to develop the computational capabilities to construct realistic models for LPS membranes with embedded outer membrane proteins for use in molecular dynamics simulations. Our focus will be on the outer membrane of P. aeruginosa, one of the most important opportunistic human pathogens, in comparison with the outer membrane of E. coil to determine the role of elements that are specifically found in the LPS structure of the outer membrane of P. aeruginosa. However, the tools and procedures that will be developed as part of the proposed work will be applicable to the study of outer """"""""membranes of any Gram-negative microbe. The goals of this proposal will be achieved through extension and implementation of new capabilities of NWChem, our massively parallel computational chemistry software suite for electronic structure calculations and classical molecular dynamics simulations.
| Straatsma, T P; Soares, T A (2009) Characterization of the outer membrane protein OprF of Pseudomonas aeruginosa in a lipopolysaccharide membrane by computer simulation. Proteins 74:475-88 |
