Asset Details
Do you wish to reserve the book?
Employing the Use of Molecular Dynamics to Explore Protein Stability and Optimize Free Energy Protocols
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Employing the Use of Molecular Dynamics to Explore Protein Stability and Optimize Free Energy Protocols
Do you wish to request the book?
Employing the Use of Molecular Dynamics to Explore Protein Stability and Optimize Free Energy Protocols
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Dissertation
Employing the Use of Molecular Dynamics to Explore Protein Stability and Optimize Free Energy Protocols
2023
Overview
Molecular dynamics (MD) is a powerful technique that can be used to provide information about a system over time. MD simulations can be used to explore behaviors of many systems such as protein-ligand interactions protein-protein interactions. Additionally, these simulations can be used to generate trajectories of a system to further be used for free energy simulations. The work discussed in Chapter 2 involves the use MD simulations to identify potential drug candidates capable of binding to and stabilizing the nuclear binding domain of the Cystic Fibrosis Transmembrane Conductance Regulator protein. Using ProBiS, we were able to find a potential binding site as well as potential small molecules to bind to said site. The stabilizing effects of these drugs were then tested experimentally using ∆F508- NBD1 expressed in E. coli. DSF experiments were conducted, ultimately revealing that two of the tested small molecules binds to our protein, but showing destabilizing effects rather than the stabilizing effects we’d hoped to see. In Chapter 3, MD simulations were used to assess the stability of a protein-protein complex, 14-3-3 and Raf. Through Molecular Dynamics simulations we found that dephosphorylation of Ser259 affected the stability of the complex, while Raf orientation had minor effects on the complex stability. Lastly, we used MD simulations in Chapter 4, as a starting point to improve free energy simulations by adopting the optimized protocols discovered by our collaborator and employing the use of force matching to improve conformational overlap between the “low level” and “high level” systems. Here, we finally achieved better convergence and configurational overlap betwixt our forcematched parameter sets and those from our higher level of theory (3OB).
Publisher
ProQuest Dissertations & Theses
Subject
ISBN
9798381156010
