Computational investigation of the Human γS-crystallin protein associated with cataracts formation

Kaiden Zaborowski
Dr. Andrew Kauffmann, Faculty Mentor

Using computational methods the human γS-crystallin dimer (PDB: 6FD8) was investigated. Dimerization of this protein occurs via an intermolecular disulfide bond at Cys24 leading to a biphasic unfolding and a high aggregation propensity in the aging lens. To begin the computational investigation, 500 ns Molecular Dynamics (MD) simulations were conducted in triplicate to evaluate the structural stability of the dimer. Then 500ns Constant pH Molecular Dynamics (CpHMD) simulations were implemented to identify the protonation states of essential aspartate residues acting as hydrogen donors near the disulfide bond. Finally, Dock6  was utilized to model the binding mechanisms of Dithiothreitol (DTT) to the γS-crystallin dimer, exploring its efficacy as a reducing agent to break the pathogenic disulfide bond. By integrating MD, cpHMD, and docking protocols, this study elucidates the dimer’s stability and provides a foundation for developing therapeutic ligands to combat oxidative protein damage within the eye lens.

Keywords: Molecular Dynamics, Molecular Docking, Constant pH Molecular Dynamics, Protein Dimerization, Disulfide Bond Reducer, Dithiothreitol, Computational Chemistry

Topic(s):Chemistry
Biochemistry and Molecular Biology
Biology

Presentation Type: Oral Presentation

Session: TBA
Location: TBA
Time: TBA