Protein folding complexity

Finding the minimum of the hybrid energy function is very complex. Similar to the protein folding problem, the number of degrees of freedom is far too large to allow a complete systematic search in all variables. Systematic search methods need to reduce the problem to a few degrees of freedom (see, e.g.. Ref. 30). Conformations of the molecule that satisfy the experimental bounds are therefore usually calculated with metric matrix distance geometry methods followed by optimization or by optimization methods alone. 

The current understanding of the protein folding process has benefited much from studies that focus on computer simulations of simplified lattice models. These studies try to construct as simple a model as possible that will capture some of the more important properties of the real polypeptide chain. Once such a model is defined it can be explored and studied at a level of detail that is hard to achieve with more realistic (and thus more complex) atomistic models. 

To conclude, although the models used in lattice simulations are very simplified, the results provide general information on possible protein folding scenarios, albeit not on the detailed behavior of specific proteins, which would require more complex models and more accurate potentials. The contribution made by these simulations is that they enable an analysis of the structures, energetics, and dynamics of folding reactions at a level of detail not accessible to experiment. 

How does the GroEL-GroES complex function as a chaperone to assist protein folding Although several aspects of the mechanism are not clear, the main features of the functional cycle are known. The first step is the... 

Mayhew, M., et al. Protein folding in the central cavity of the GroEE-GroES chaperonin complex. Nature 379 420-426, 1996. 

Proteins are complex molecules that give cells structure and act as both enzymes and motors within cells. Proteins are long strings of amino acids folded in specific three-dimensional formations. There are twenty different animo acids in our bodies. DNA, the genetic material located in the cell nucleus, carries information for the order of the amino acids in each protein. Indeed, in the simplest sense, a gene is the... 

Ostermann, J., Horwich, A.L., Neupert, W., Hartl, F.-U. (1989). Protein folding in mitochondria requires complex formation with hsp60 and ATP hydrolysis. Nature 341, 125-130. 

Fraenkel, A.S. (1993) Complexity of protein folding, Bull. Math. Biol., 55, 1199-1210. 

For the first group (i.e. intracellular soluble enzymes and proteins), which need no posttranslational modification and complex domain organization influencing protein folding, E. coli is the most preferred choice. However, for the other targets, alternative expression systems often provide a higher rate of success. The most common expression systems are presented in this chapter. 

---