Protonation States and Conformations of Inositol and Phosphoinositol Phosphates from Molecular Simulations

Biophysical Journal 116 (3), 506a-507a

Authors: B. K. Radak

Phosphoinositide phosphates (PIPs) are ubiquitous components in numerous cell signaling pathways. However, there is currently a considerable lack of detailed atomistic models for how PIPs interact with their environment, especially with kinase and phosphatase proteins. While it is well- documented that molecular recognition of PIPs depends on the specific num- ber of phosphorylated sites (one to three), the protonation state of each phos- phate is also a critical component. Indeed, this clearly has an effect on the specific protein-lipid binding pose. Nonetheless, there have been very few studies of how these protonation states change between bound/unbound states or even when a PIP is in a membrane versus free in solution. Here we present constant-pH molecular dynamics simulations of various PIP- related compounds in order to analyze correlations between their pKa values, structure, and environment.

Biophysical Journal