Computational Analysis of Crosslinking Agents With SOD1 in ALS to Inhibit Aggregation
MetadataShow full item record
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease that affects the motor neurons in the brain and spinal cord with no effective medication to halt or reverse the symptoms. Although most ALS cases are sporadic and have no known cause, a significant percentage of cases have a genetic association that is caused by the subsequent unfolding and aggregation of superoxide dismutase [Cu, Zn] homodimer. The Ondrechen Research Group has been in works to identify potential cyclic disulfide crosslinking agents to stabilize the ALS associated protein by “tethering” two SOD1 monomers via adjacent Cys111 resides using maleimide chemistry. Initial computational homology modeling, docking simulations, and analyses were conducted to find potential crosslinking agents among 53 cyclic disulfides using YASARA. The initial research resulted in identifying, in total, seven cyclic disulfides as potential crosslinking agents. A couple cyclic disulfides have been computationally determined to be able to stabilize more than one SOD1 variant.