Computational studies of cyclic peptides, potassium channels and self-assembled 2D crystals
Abstract: Cyclic peptides are an interesting class of molecules that have a
wide variety of applications, including nanotechnology and therapeutics. The full potential
of cyclic peptides, however, has not been realized, as studies of their sequence-structure
relationships are lacking. Understanding how the sequence affects the structure of a cyclic
peptide will significantly aid in their rational ... read moredesign. The work described in the first
few Chapters aims to develop a better understanding of cyclic penta-, hexa- and
heptapeptides using computer simulations. Chapter 2 explores the sequence-structure
relationships of cyclic pentapeptides. From simulations and neighbor interaction analysis
we found several cyclic pentapeptides that are predicted to be well-structured from both
simulations and experiments. Chapter 3 describes systematic studies of cyclic
heptapeptides, in order to design and optimize a cyclic heptapeptide for experimental
verification. Additionally, since N-methylation has been shown to improve the
bioavailability of cyclic peptides, Chapter 4 shows how well two current peptide force
fields are able to recapitulate the NMR structures of several N-methylated cyclic penta-
and hexapeptides. Additionally, Chapter 5 explores the applicability of a few small
molecule drugs at targeting an inwardly rectifying potassium channel as a potential
therapeutic for atrial fibrillation, through a combination of simulation and experimental
techniques. Chapter 5 also describes how several modifications of the potassium channel
affect its structure and dynamics. Finally, Chapter 6 describes correlated switching
observed in self- assembled two-dimensional crystals, through a combination of scanning
tunneling microscopy experiments, statistical analysis and Monte Carlo simulations. Through
the analysis of several different molecules, Chapter 6 shows that the self- assembled
structure dictates the correlated switching pattern.
Thesis (Ph.D.)--Tufts University, 2017.
Submitted to the Dept. of Chemistry.
Advisor: Yu-Shan Lin.
Committee: Arthur Utz, Mary Jane Shultz, and Bradley Pentelute.
Keywords: Chemistry, Physical chemistry, and Biophysics.read less