Spatial Organization of Biological Fuctions | BPS Thematic Meeting

Spatial Organization of Biological Functions Meeting

Poster Abstracts

15-POS Board 15 MOLECULAR DYNAMICS SIMULATIONS TO PROBE THE ROLE OF ABNORMAL WATER ACCESS IN G90D RHODOPSIN-LINKED CONGENITAL STATIONARY NIGHT BLINDNESS (CSNB) Kunal Rai 1 ; 1 Indian Institute of Technology, Hyderabad, India, Department of Physics, Department of Biotechnology, Kandi, Sangareddy, India Rhodopsin, the prototypical G protein-coupled receptor (GPCR) of rod photoreceptor cells, is responsible for dim-light vision by triggering the visual transduction cascade. Although a majority of rhodopsin mutations cause misfolding or trafficking defects that form the basis of retinitis pigmentosa, the G90D mutation causes congenital stationary night blindness (CSNB), a non-degenerative disease characterized by fixed night blindness and dark-state signaling. Experimental evidence indicates that G90D disrupts the electrostatic environment around the Schiff base lysine (K296), disrupting its interaction with E113 and enhancing water accessibility to the chromophore-binding pocket. This disease-causing hydration may destabilize inactive dark-state rhodopsin, resulting in spontaneous low-level activity and physiological "noise" in the absence of light. Here, we intend to investigate these mechanistic hypotheses with all-atom molecular dynamics (MD) simulations. We will simulate wild-type and G90D rhodopsin in multiple ligand states (11-cis, all-trans, and naked) embedded in explicit lipid bilayers. The simulations will quantify water access pathways, Schiff base dynamics, hydrogen bonding patterns, and conformational shifts toward activation. Comparative simulations of cone opsins (M- and S-opsin) will further explore hydration-mediated functional differences. These simulations will clarify the structural basis of G90D-linked CSNB and advance our understanding of hydration-driven modulation in visual GPCRs.

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