A molecular dynamics investigation of lipid bilayer perturbation by PIP2

Dmitry Lupyan, Mihaly Mezei, Diomedes E. Logothetis, Roman Osman

Research output: Contribution to journalArticlepeer-review

70 Scopus citations


Phosphoinositides like phosphatidylinositol 4,5-bisphosphate (PIP 2) are negatively charged lipids that play a pivotal role in membrane trafficking, signal transduction, and protein anchoring. We have designed a force field for the PIP2 headgroup using quantum mechanical methods and characterized its properties inside a lipid bilayer using molecular dynamics simulations. Macroscopic properties such as area/headgroup, density profiles, and lipid order parameters calculated from these simulations agree well with the experimental values. However, microscopically, the PIP2 introduces a local perturbation of the lipid bilayer. The average PIP2 headgroup orientation of 45° relative to the bilayer normal induces a unique, distance-dependent organization of the lipids that surround PIP2. The headgroups of these lipids preferentially orient closer to the bilayer normal. This perturbation creates a PIP2 lipid microdomain with the neighboring lipids. We propose that the PIP2 lipid microdomain enables the PIP2 to function as a membrane-bound anchoring molecule.

Original languageEnglish
Pages (from-to)240-247
Number of pages8
JournalBiophysical Journal
Issue number2
StatePublished - 20 Jan 2010


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