Vision, molecular events

We have discussed only the visual aspects of the fourth vision. Auditory phenomena are of equal importance. Here the solid, labelled nature of auditory patterns is lost, and the mechanical impact of sound hitting the eardrum is registered. In some cases, sound becomes converted into pure sensation, and synesthesia (mixture of sense modalities) occurs. Sounds are experienced as colors. External sensations hitting the cortex are recorded as molecular events, ineffable. 

Our analysis of the possible role of the ERP suggests another attribute of intelligent materials that is, modular design of molecular functions. The ability of bacteriorhodopsin to bind protons from the cytoplasm upon light stimulation serves as a critical step in proton translocation. The same event in rhodopsin, however, may serve an entirely different function it triggers the cyclic GMP cascade. Thus, Nature could well have utilized a common design for vision and for photosynthesis (85). The same design principle may be implemented with completely different types of molecules or materials. On the other hand, the same molecular event may be exploited for different purposes. 

Research into the molecular events taking place in the process of vision, is closely connected with the name of George Wald. The lecture he gave when he received the Nobel price is a beautiful review of the subject [2]. (See Heller [3] for a recent review.)... 

Gascon JA, Batista VS (2004) QM/MM study of energy storage and molecular rearrangements due to the primary event in vision. Biophys. J. 87(5) 2931-2941... 

Hayashi S, Tajkhorshid E, Schulten K (2009) Photochemical reaction dynamics of the primary event of vision studied by means of a hybrid molecular simulation. Biophys J 96 403 16... 

Another level of enhanced effort will be in the area of epidemiology, both traditional and molecular, and human in vitro research in support of the identification of key events in humans and of the human relevance of an animal MoA. The recently published National Research Council (NRC) Report, Toxicity Testing in the 21st Century A Vision and a Strategy (NRC 2007), provides a set of research options for enhancing the use of in vitro test systems with an emphasis on human cells. This... 

The protonated Schiff base of 11-cis-retinal (PSBll) is the chromophore in the visual receptor rhodopsin. A light-induced cisitrans isomerization of the chromophore triggers the primary event in vision, which is a series of conformational changes of the protein. This photoreaction is considered as the archetype of a chemical reaction optimized by nature to achieve a specific molecular response. Hence, it was in focus of numerous computational and experimental investigations. 

However, dielectric solvation models do suffer from a too simple description of the solute-solvent interactions, and also from a static vision of the solvated system, which is supposed to be at thermodynamic equilibrium. A step forward was done after the publication in 1990 of a paper by Field et al. [19] on the QM/MM model, which was an extension of the seminal work reported by Warshel and Levitt in 1976 [20] (the acronym QM/MM stands for Quanmm Mechanics/Molecular Mechanics). The QM/MM model was initially developed to carry out Molecular Dynamics (MD) simulations of large molecules such as proteins using a semi-empirical description of the active site. But extension to first-principles studies of ions and molecules in solution [21-23] was reported soon after Karplus work and algorithms to simulate chemical reaction trajectories and analyze non-equilibrium effects in solution based on a rare event sampling approach were developed [24, 25]. 

Mathies, R.A., Photons, femtoseconds and dipolar interactions a molecular picture of the primary events in vision, in Rhodopsins and PhototransducHon, John Wiley Sons, New York, 1999, p. 70. 

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