Study of the γD-Crystallin Protein Using Two-Dimensional Infrared (2DIR) Spectroscopy: Experiment and Simulation

Cataracts is a misfolding protein disease in which one of its major components is the γD-crystallin protein. The conformational structure of the aggregated γD-crystallin and the interactions that cause aggregation are largely unknown. A recent experimental two-dimensional infrared (2DIR) spectroscopy study determined that the C-terminal domain has a high propensity to form β-sheets whereas the N-terminal domain forms a disordered structure in the fiber state. We present a combined computational molecular dynamics (MD) and infrared spectroscopy study of the local dynamics of these domains. The computed 2DIR signals agree remarkably well with experiment. We show that both domains having a Greek key structural fold experience different electrostatic environments, which may be related to the fact that the C-terminal domain is more structurally stable than the N-terminal domain. We correlate the vibrational couplings to known energy dissipation mechanisms and reveal their origin