The chemical physics of life as we know it involves a myriad of reactions which proceed with remarkable efficiency and selectivity, rarely duplicated in nonbiological systems. The reason for this is that biochemical reactions proceed in the highly organized environment of proteins whose architecture at the active center determines their chemical behaviour. The structure of a protein, therefore, determines its function.

Static structures determined at atomic resolution using X-ray crystallography can reveal the relative proximity and orientation of functional groups and can help to rationalize a protein's chemical activity. However, a deeper understanding of protein function requires extending our present three-dimensional picture of proteins to the fourth dimension, i.e. time. This requires the determination of the reaction coordinate for functional electronic and coupled conformational change in proteins together with the associated energetics. 

A detailed understanding of reaction dynamics requires knowledge of both electronic and nuclear motion along the predominant reaction pathway. Obtaining this level of understanding will require contributions from physics aimed at understanding the molecular dynamics and quantum mechanics of proteins. An important step in this  direction has been the experimental use of physical and chemical trapping methods to capture and then freeze reaction intermediates in crystals. Subsequently, the combination of diffraction methods with spectroscopic techniques provides a means to directly correlate electronic transitions with structural reorientations in the sample. For certain protein systems that have been studied in depth the information thus obtained is at a level where the development and application of complementary theoretical techniques is required to push our understanding further. The insight thus obtained may eventually allow the design of new protein sequences that fold into target structures and execute a designed function and may also help to assess the function of proteins that have been discovered as a consequence of sequencing the human genome.

The retinal proteins are particularly well suited for in-depth physical study of functional mechanisms at atomic detail. Among these, the best studied so far is bacteriorhodopsin (bR). bR is the prototype of a membrane transporter, that is, a biological macromolecule performing the difficult task of transporting ions against an electrochemical potential - up to 250 millivolts in the case of bacteriorhodopsin, which translates into a 10,000-fold difference in proton concentration on either side of the membrane. Such transport processes are fundamental to all forms of life. Therefore, in addition to the more general aim of understanding protein reaction profiles, studies of this protein promise a better understanding of how ion pumps function.

Rhodopsin (Rh), another retinal protein, is a member of the super-family of G-protein coupled receptor (GPCR) proteins, which activate cellular pathways in response to external signals. Up to 3% of the human genome is used to encode GPCRs, which are stimulated by simple ions, amines, hormones, odors, neurotransmitters, or even light. Binding of the ligand, or light-induced isomerization of the chromophore, activates the protein signaling state, which binds G-protein and initiates, in the case of rhodopsin, the so-called visual cascade. G-protein coupled receptors share with bacteriorhodopsin the structural motif of seven trans-membrane helices. Determining in atomic detail the fate of the excited chromophore and how it transforms rhodopsin into the active state would be a key step in understanding the process of vision and GPCR action in general.