AutoCAD 2014

Molecular Biophysics of Vision

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The understanding of the molecular mechanisms involved in light detection is an challenging task for the science of vision, that has important implication from both the medical and technological point of views. The first step in the eye detection of light is the photo-excitation of the receptor cells (rod and cones) in the retina. The rod cells, responsible for the peripheral and night vision, accomplish this function using as a fundamental detector the integral membrane protein rhodopsin (Fig. A). In normal conditions, photons excite the rhodopsin chromophore moiety, the retinal, inducing a cis to trans isomerization (Fig. B) that provokes allosteric changes in the protein. These modification causes G-protein binding at the rhodopsin cytoplasmic side, triggering a complex signal transduction cascade of signalling, finally leading to neuronal signal and vision. The failures of proper synthesis, processing or functioning of this signal transduction machinary are involved in the pathogenesis of many eyes diseases, such as the class of hereditary progressive blinding diseases Retinis Pigmentosa.

rh1

 

 A) The rhodopsin protein is represented by light blue tubes and ribbons whereas its photoactive moiety (the retinal chromophore) is represented by yellow sticks. 
 B) The rodopsin retinal protonated Schiff base undertakes a 11-cis to all-trans isomerization upon photon absorption. 

 

In the first femtoseconds of their photocycle, the retinal are isomerized by light absorption around a C-C double bond, leading to local change in the protein surroundings. The initial movements are therefore transmitted to the protein-wide scale, and converted in significant structural changes and biological signal. With classical MD, QM/MM, and TDDFT we have investigated the very first movements upon light absorption as well as the subsequent protein relaxation [10,14,17].

 

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