TY - JOUR
T1 - Modeling Diversity in Structures of Bacterial Outer Membrane Lipids
AU - Ma, Huilin
AU - Cummins, Daniel D.
AU - Edelstein, Natalie Brooke
AU - Gomez, Jerry
AU - Khan, Aliza
AU - Llewellyn, Masud Dikita
AU - Picudella, Tara
AU - Willsey, Sarah Rose
AU - Nangia, Shikha
N1 - Funding Information:
The authors thank the XSEDE Supercomputing Facility and Information and Technology Services at Syracuse University (Eric Sedore, Larne Pekowsky, and Michael R. Brady) for providing computational resources for some of the simulations presented here. The authors also thank various funding sources that funded one or more undergraduate students for this project. We thank National Science Foundation (NSF) for providing financial support for S.R.W., T.P., and M.D.L. (Grant EFRIMIKS-1137186) and D.D.C. (REU, NSF DMR-1460784; the Student Association, the Vice Chancellor and Provost for Academic Affairs, the Associate Provost for Academic Programs, the Vice President for Research, and the New York State Collegiate Science and Technology Entry Program at Syracuse University for J.G.; Syracuse University’s College of Engineering and Computer Science Dean’s Leadership Fund for N.B.E.; and Syracuse University for A.K. and H.M.
Publisher Copyright:
© 2017 American Chemical Society.
PY - 2017/2/14
Y1 - 2017/2/14
N2 - Lipopolysaccharides (LPSs) are vital components of the outer membrane of Gram-negative bacteria, and they act as extremely strong stimulators of innate immunity in diverse eukaryotic species. The primary immunostimulatory center of the LPS molecule is lipid A, a disaccharide-bound lipophilic domain. Considering the broad diversity in bacterial species, there are variations in the lipid A structures and their immunogenic potencies. In this work, we model the lipid A structures of eight commensal or human pathogenic bacterial species: Helicobacter pylori, Porphyromonas gingivalis, Bacteroides fragilis, Bordetella pertussis, Chlamydia trachomatis, Campylobacter jejuni, Neisseria meningitidis, and Salmonella Minnesota. The membrane properties of these bacterial species were characterized and compared using molecular simulations. The structure-property relationships that emerge from this lipid A molecular library highlight the roles of acyl chain lengths, number of chains, phosphorylation state, membrane composition, and counterion charge in regulating the phase transition temperature of the membrane, diffusion coefficient of the lipids, and membrane thickness. The molecular and structural insights provided reveal the diversity in bacterial outer membrane lipids and their contribution to human disease and immunity.
AB - Lipopolysaccharides (LPSs) are vital components of the outer membrane of Gram-negative bacteria, and they act as extremely strong stimulators of innate immunity in diverse eukaryotic species. The primary immunostimulatory center of the LPS molecule is lipid A, a disaccharide-bound lipophilic domain. Considering the broad diversity in bacterial species, there are variations in the lipid A structures and their immunogenic potencies. In this work, we model the lipid A structures of eight commensal or human pathogenic bacterial species: Helicobacter pylori, Porphyromonas gingivalis, Bacteroides fragilis, Bordetella pertussis, Chlamydia trachomatis, Campylobacter jejuni, Neisseria meningitidis, and Salmonella Minnesota. The membrane properties of these bacterial species were characterized and compared using molecular simulations. The structure-property relationships that emerge from this lipid A molecular library highlight the roles of acyl chain lengths, number of chains, phosphorylation state, membrane composition, and counterion charge in regulating the phase transition temperature of the membrane, diffusion coefficient of the lipids, and membrane thickness. The molecular and structural insights provided reveal the diversity in bacterial outer membrane lipids and their contribution to human disease and immunity.
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U2 - 10.1021/acs.jctc.6b00856
DO - 10.1021/acs.jctc.6b00856
M3 - Article
C2 - 28080049
AN - SCOPUS:85012918319
SN - 1549-9618
VL - 13
SP - 811
EP - 824
JO - Journal of Chemical Theory and Computation
JF - Journal of Chemical Theory and Computation
IS - 2
ER -