Filip Dinic1, Anita Rágyanszki2, Natalie J. Galant3, Imre G. Csizmadia1,2
1Department of Chemistry, University of Toronto
2Department of Chemical Informatics, Faculty of Education, University of Szeged
3Department of Medical Biophysics, University of Toronto
Corresponding Author: Filip Dinic (email@example.com)
Previous studies have demonstrated that the ring flips undergone by vicinal disulfide rings (VDR) play a significant role in the bonding function of nicotinic acetylcholine receptor’s (nAChR), whereas due to the change in confirmations, the nAChR will also undergo a change in shape. These nAChR’s are mainly found in axon terminals, and have a role in nicotine addiction and diseases such as Parkinson’s and Alzheimer’s. These receptors are potential drug targets, and understanding the change in properties as the ring flips between its conformers can lead to potential drugs which could minimize or prevent these illness from occurring. This ab initio study investigates the nature of various eight-membered rings and their associated ring flips, quantifying and analyzing its effects of thermodynamics and structure. It was determined that while this process is spontaneous the associated activation energy with this transition is high. In addition, the S-S linkage was found to impose a great deal of strain, leading to deformation of the ring. This study elucidates the process of various eight membered ring flips, allowing for a better understanding of its influence on nAChR’s.