Date of Graduation
Eberly College of Arts and Sciences
Peptides with the ability to bind and insert into the cell membrane are an ever-growing field of research due to their potential biomedical applications. pH (Low) Insertion Peptide (pHLIP), which is a water-soluble polypeptide derived from helix C of bacteriorhodopsin, has the ability to insert into a membrane at acidic pH to form a stable transmembrane alpha-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 alpha-helix at low pH (state III). It has been shown that pHLIP binding and insertion occurs over large timescales and multiple kinetic steps from state I to state III. Our study focuses on the initial step, uncoiled pHLIP binding to a lipid bilayer surface, using enhanced sampling molecular dynamics simulation techniques. We have quantified the thermodynamics of this process by computing the free energy change upon binding of a pHLIP variant at several orientations to model lipid bilayers. In addition, our studies provide atomistic details about the binding behaviors of pHLIP to a lipid bilayer that provide a fundamental understanding of the biophysical underpinnings of the pHLIP mechanism.
Ren, Yue, "Using enhanced sampling molecular dynamics to probe the binding process of the membrane insertion peptide pHLIP" (2015). Graduate Theses, Dissertations, and Problem Reports. 6492.