Understanding nature's design for a nanosyringe
- Center for Molecular Modeling, Chemistry Department, University of Pennsylvania, 231 South 34th Street, Philadelphia, PA 19104-6323
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Communicated by William F. DeGrado, University of Pennsylvania School of Medicine, Philadelphia, PA, January 15, 2004 (received for review November 1, 2003)
Abstract
Synthetic and natural peptide assemblies can possess transport or conductance activity across biomembranes through the formation of nanopores. The fundamental mechanisms of membrane insertion necessary for antimicrobial or synthetic pore formation are poorly understood. We observe a lipid-assisted mechanism for passive insertion into a model membrane from molecular dynamics simulations. The assembly used in the study, a generic nanotube functionalized with hydrophilic termini, is assisted in crossing the membrane core by transleaflet lipid flips. Lipid tails occlude a purely hydrophobic nanotube. The observed insertion mechanism requirements for hydrophobic-hydrophilic matching have implications for the design of synthetic channels and antibiotics.
Footnotes
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↵ † To whom correspondence may be addressed. E-mail: lopez{at}cmm.upenn.edu or klein{at}lrsm.upenn.edu.
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↵ ‡ Present address: Department of Pharmacy, University of the Sciences in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104-4495.
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Abbreviations: NT, hydrophobic cylindrical macromolecule; NT*, hydrophobic macromolecule with hydrophilic caps; MD, molecular dynamics; DMPC, dimyristoylphosphatidylcholine; CG, coarse-grain.
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See Commentary on page 4337.
- Copyright © 2004, The National Academy of Sciences
