Biophys J, December 2002, p. 3097-3112, Vol. 83, No. 6

Molecular Dynamics Investigation of Primary Photoinduced Events in the Activation of Rhodopsin

Jan Saam,^* Emad Tajkhorshid,^* Shigehiko Hayashi,^* and Klaus Schulten^*

 ^*Beckman Institute, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 USA;  Department of Biology, Humboldt University Berlin, 10999 Berlin, Germany; and  Department of Physics, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801 USA

Retinal cis-trans isomerization and early relaxation steps have been studied in a 10-ns molecular dynamics simulation of a fully hydrated model of membrane-embedded rhodopsin. The isomerization, induced by transiently switching the potential energy function governing the C₁₁==C₁₂ dihedral angle of retinal, completes within 150 fs and yields a strongly distorted retinal. The most significant conformational changes in the binding pocket are straightening of retinal's polyene chain and separation of its -ionone ring from Trp-265. In the following 500 ps, transition of 6s-cis to 6s-trans retinal and dramatic changes in the hydrogen bonding network of the binding pocket involving the counterion for the protonated Schiff base, Glu-113, occur. Furthermore, the energy initially stored internally in the distorted retinal is transformed into nonbonding interactions of retinal with its environment. During the following 10 ns, increased mobilities of some parts of the protein, such as the kinked regions of the helices, mainly helix VI, and the intracellular loop I2, were observed, as well as transient structural changes involving the conserved salt bridge between Glu-134 and Arg-135. These features prepare the protein for major structural transformations achieved later in the photocycle. Retinal's motion, in particular, can be compared to an opening turnstile freeing the way for the proposed rotation of helix VI. This was demonstrated by a steered molecular dynamics simulation in which an applied torque enforced the rotation of helix VI.

Biophys J, December 2002, p. 3097-3112, Vol. 83, No. 6
© 2002 by the Biophysical Society   0006-3495/02/12/3097/16  $2.00

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