Other Aspects of Protein Modeling

If nothing is known about the tertiary structure of the protein of interest, can anything be done to develop a reasonable model As mentioned earlier, complete searching of conformational space is impossible for proteins and other large molecules. However, several groups have developed methods to simplify the problem into one that is solvable. 

Another way to simplify the tertiary structure problem is to fix the backbone and then carry out an exhaustive search on the allowed side chain conformations. Desmet and co-workers have developed a dead-end elimination method for searching side chain conformations. Side chain conformations are grouped into a limited set of allowed rotamers. While an exhaustive search of all possible combinations of these rotamers is still not feasible, the application of the dead-end elimination theorem allows removal of impossible combinations early in the search, thus controlling the combinatorial explosion and leading to a small group of possible final solutions. The possible solutions can then be compared to find the best possible structure. 

It should also be mentioned that Scheraga and co-workers have developed numerous methods that have solved the multiple minima problem for oligopeptides. Excellent agreement between predicted and observed conformations is possible. These methods, which are applicable to building small proteins, were reviewed in 1992.  

Modeling is used by researchers who are trying to understand protein folding that is. Why does a given sequence always fold into the same three-dimensional shape. The ultimate goal is to be able to predict the tertiary struaure of a protein from its amino acid sequence. Ideally, both the backbone 

Molecular modeling is also used in protein engineering to modify specifically or randomly selected residues of a protein to change the substrate specificity or to try to find an amino acid sequence that will fold into a specific, preselected 3D shape (the inverse protein folding problem). An introduction to this topic has been written by van Gunsteren. xhe principles of modeling have also been used to design new enzymes with altered substrate specificity. -  

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