Event
Biophysics Seminar
Monday, May 9, 2016
4:00 p.m.-5:00 p.m.
0112 CHEM
Blake Mertz, West Virginia University
Probing membrane binding of the pH low insertion peptide with molecular simulations
Peptides with the ability to bind and insert into the cell membrane have immense potential in biomedical applications. pH (Low) Insertion Peptide (pHLIP), a water-soluble polypeptide derived from helix C of bacteriorhodopsin, can insert into a membrane at acidic pH to form a stable transmembrane α-helix. The insertion process takes place in three stages: pHLIP is unstructured and soluble in water at neutral pH (state I), unstructured and bound to the surface of a membrane at neutral pH (state II), and inserted into the membrane as an α-helix at low pH (state III). Using molecular dynamics (MD) simulations, we have modeled state II in which a coiled pHLIP variant is bound to a 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) bilayer surface. Our results provide strong support for recently published spectroscopic studies, namely that pHLIP preferentially binds to the bilayer surface as a function of location of anionic amino acids and that backbone dehydration occurs upon binding. Our results provide a molecular level of detail that is essential to our understanding of pHLIP function and the ability to design pHLIP variants with improved efficiency in drug delivery and diagnostic imaging applications.
