Intracellular proteins participate in most cellular processes,
operating at the molecular level. Obvious examples are enzymes
which facilitate molecular reactions by decreasing the activation
energy via transition state stabilization. Enzyme-catalyzed reactions have a plethora of applications ranging from
medicine related fields to industrial processes and agriculture(Walsh,
2001). The ability to genetically engineer cells and produce
recombinant proteins in large scale allows taking full advantage
of bio-based processes. Such processes are increasingly important
in modern society and thus our ability to understand how
enzymes operate is becoming more valuable. The complex
chemical structure of proteins and the interplay of individual amino acid residues represent a huge obstacle for this understanding.
Biophysical methods,such as X-ray crystallography and nuclear
magnetic resonance,are useful to deduce the spatial arrangement
of amino acid residues in proteins, which can be further expanded
through homology models for similar proteins (BurleyandBonanno,
2002). But these techniques can not be universally applied, and a
significant number of proteins still do not benefit from the break-
throughs in structural biology. This is clearly observed for integral
membrane proteins, whose structure determination usually require
many ancillary experiments and well-developed prediction
algorithms(vonHeijne,2011). Eventhen, determining the structure of
a protein at high resolution does not necessarily help to decipher the
molecular mechanisms controlling its functions.