Theoretical and computational modeling of peptide-lipid bilayer interaction studied by dynamic force spectroscopy

This thesis consists of three interrelated theoretical and computational modeling projects that investigate different aspects of peptide-lipid membrane interactions. (1) A general theoretical approach is formulated for the quantitative description of the detachment force distribution, P(F), and the corresponding force dependent detachment rate, k(F), of a peptide from a lipid bilayer, by assuming that peptide detachment from lipid membranes occurs stochastically along a few dominant diffusive pathways. Besides providing a consistent interpretation of the experimental data, the new method also predicts that k(F) exhibits catch-bond behavior (when, counter intuitively, the detachment rate decreases with increasing force). (2) The proposed multiple detachment pathways method is tested and validated for a particular peptide (SecA2-11) interacting with both zwitterionic POPC lipid and polar E. Coli membranes. Furthermore, molecular dynamics (MD) simulations are used to explored the conformational dynamics of SecA2-11 during its interaction with both POPC and anionic POPG lipid bilayers. (3) Finally, MD simulations are used to explore the conformational dynamics and energetics of the peptide melittin (MWT) and its diastereomer (MD4) interacting with POPC and POPG lipid bilayers. The obtained results provide further insight into the role of secondary structure in peptide-lipid bilayer interactions.

Name thesis:degree_name

Ph. D.

Level thesis:degree_level

Doctoral

Discipline thesis:degree_discipline

Physics and astronomy (MU)

Grantor dc:publisher

University of Missouri--Columbia

Year dc:date.issued

2019

Author dc:creator

• Utjesanovic, Milica

Advisor dc:contributor.advisor

• Kosztin, Ioan

Statement dc:rights

• OpenAccess.

Language dc:language.iso

eng, English

DOI

https://doi.org/10.32469/10355/76254

OAI identifier oai:identifier

oai:mospace.umsystem.edu:10355/76254