Presentation Title

A molecular dynamics study on pH-low insertion peptides at different charge states in varying membrane compositions

Presenter Information

Brandon BogartFollow
Afra PanahiFollow

Faculty Mentor

Afra Panahi

Start Date

23-11-2019 8:45 AM

End Date

23-11-2019 9:30 AM

Location

204

Session

poster 2

Type of Presentation

Poster

Subject Area

interdisciplinary

Abstract

pH-low insertion peptides (pHLIP) have become of interest due to their pH dependent structure. At a neutral pH, pHLIP will bind to a membrane surface interfacially, while exhibiting an unstructured conformation. When in an acidic environment, pHLIP spontaneously insert themselves into the membrane bilayer and adopt a transmembrane helix structure. This property of pHLIP have proven to be a promising tool in targeted drug delivery, such as to solid tumors which are known to be acidic. However, currently little is known about the mechanistic pathway in which pHLIP adapt to pH and their membranes. In order to improve the selectivity and efficacy of pHLIP as targeted cargo delivery tool, more must be understood about their specific innerworkings. In order to gain detailed structural insight about pHLIP, this work employs the use of all-atom molecular dynamics (MD) simulations. Different charge states of pHLIP in multi-component membrane bilayers were simulated and the time evolution of the peptide was carefully analyzed. From these simulations, in agreement with earlier circular dichroism studies, it was found that when aspartic (D) and glutamic acids (E) are in their protonated states, the peptide maintains its helical state regardless of the composition of the bilayer. However, the peptides structure depict more sensitivity to the membrane when D and E are in their charge state.

This document is currently not available here.

Share

COinS
 
Nov 23rd, 8:45 AM Nov 23rd, 9:30 AM

A molecular dynamics study on pH-low insertion peptides at different charge states in varying membrane compositions

204

pH-low insertion peptides (pHLIP) have become of interest due to their pH dependent structure. At a neutral pH, pHLIP will bind to a membrane surface interfacially, while exhibiting an unstructured conformation. When in an acidic environment, pHLIP spontaneously insert themselves into the membrane bilayer and adopt a transmembrane helix structure. This property of pHLIP have proven to be a promising tool in targeted drug delivery, such as to solid tumors which are known to be acidic. However, currently little is known about the mechanistic pathway in which pHLIP adapt to pH and their membranes. In order to improve the selectivity and efficacy of pHLIP as targeted cargo delivery tool, more must be understood about their specific innerworkings. In order to gain detailed structural insight about pHLIP, this work employs the use of all-atom molecular dynamics (MD) simulations. Different charge states of pHLIP in multi-component membrane bilayers were simulated and the time evolution of the peptide was carefully analyzed. From these simulations, in agreement with earlier circular dichroism studies, it was found that when aspartic (D) and glutamic acids (E) are in their protonated states, the peptide maintains its helical state regardless of the composition of the bilayer. However, the peptides structure depict more sensitivity to the membrane when D and E are in their charge state.