Structural Analysis of the Interactions Between Collagen and Collagen-Binding Proteins
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Collagen plays several key roles in cell binding, tissue growth, and structural strengthening of the body. We chose to study three proteins: OSCAR, DDR2, and α-1 integrin. These protein and protein domain models were built through CHARMM scripts by simulations in aqueous, ionized, heated, and energy minimized solutions. These structures were visualized in VMD. Production simulations were then performed on Texas A&M High Performance Research Computing clusters to achieve reasonable statistical trajectories for 10 ns. During the simulations, DDR2 and human OSCAR were found to be stable structures. α-1 integrin was found to be unstable because it possessed only a single high occupancy hydrogen bond between itself and collagen. During its simulation, we saw signs of dissociation, and suspect that the collagen would have fully dissociated had the simulation continued past 10 ns. This stability problem was emphasized further by the significant difference in the patterning of α-1 integrin’s RMSF and B-Factor values. DDR2 and OSCAR had similar patterns between their RMSF and B-Factor values, indicating similar stability to their original coordinates. As such, further analysis was only carried out on DDR2 and OSCAR. Looking at the distances between collagen strands for DDR2 and OSCAR models, we saw a large distance at the C and N terminals due to the end effect. All of the distances in the central regions of the collagen were roughly 5 Å apart consistently. This indicated that the structures were stable and there were no dissociations between individual collagen strands for DDR2 and OSCAR over the 10 ns simulation. The torsional angles of triads, explained in the methods, were found for DDR2 and OSCAR. Unwinding behavior was generally found within the segments of collagen that bind to DDR2 and OSCAR. This was identified as a decrease in torsional angle. Further analysis was used to determine the stability of these torsional angles over time. Generally, more hydrogen bonds between each triad and DDR2/OSCAR increased the stability of the torsional angle while unwinding the collagen fibril. Steric stabilization due to protein pockets in DDR2 and OSCAR also aided in torsional angle stabilization.
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Tang, Michael; Kim, Aaron; Hsu, Mitchell (2020). Structural Analysis of the Interactions Between Collagen and Collagen-Binding Proteins. Undergraduate Research Scholars Program. Available electronically from https : / /hdl .handle .net /1969 .1 /188413.