Proteins function evolution

Determination of Protein Function, Evolution and Interactions by Structural Genomics. 

Therein lies the secret of the diversity of protein functions. There are so many possible protein structures that nature, through the process of evolution, has been able to pick and choose among this cornucopia of possibilities to find the cream of the cream for each function. The number of different proteins in the human body— perhaps 100,000—is an incredibly small fraction of all the proteins that one can construct using 20 natural amino acids linked in chains, say, 100 units long (1 part in 10 ). 

Skolnick J, BryKnski M (2009) FINDSITE a combined evolution/structure-based approach to protein function prediction. Brief Bioinform 10 378-391... 

Moore, J.C., Jin, H.M., Kuchner, O. and Arnold, F.H. (1997) Strategies for the in vitro evolution of protein function enzyme evolution by random recombination of improved... 

Evolution has not taken a simple linear path. Complexities abound in any attempt to mine the evolutionary information stored in protein sequences. For a given protein, the amino acid residues essential for the activity of the protein are conserved over evolutionary time. The residues that are less important to function may vary over time—that is, one amino acid may substitute for another—and these variable residues can provide the information used to trace evolution. Amino acid substitutions are not always random, however. At some positions in the primary structure, the need to maintain protein function may mean that only particular amino acid substitutions can be tolerated. Some proteins have more variable amino acid residues than others. For these and other reasons, proteins can evolve at different rates. 

Molecular evolution demands inherent self-reproductivity. RNA seems to fulfill this function best of all known macromolecules. On account of its complex structure RNA must first have appeared in nature long after proteins or protein-like structures. A protein can by chance fulfill a particular function, but this fulfilment is determined by purely structural and not at all by functional criteria. Adaptation to a particular function, however, demands an inherent mechanism of self-reproduction. The only logically justifiable way of exploiting the immense functional capacity of the proteins in evolution lies in an intermarriage between these two classes of macromolecules, that is, in the translation into protein of the information stored in the self-reproductive RNA structures. 

M. Ostermeier and S.). Benkovic, Evolution of protein function by domain swapping, Adv. Protein Chem. 2000, 55, 29-77. 

Zuckerkandl E. The appearance of new structures and functions in proteins during evolution. J Molec Evol 1975 7 1. 

Although the comparisons of protein folds can yield valuable insights into protein function and evolution, it is also very desirable to be able to detect structural similarities at the residue or atomic level. This is because the detection of similar patterns of functional groups in different proteins may allow analogies to be drawn between disparate proteins modes of action. The classic example of this are the similar clusters of three catalytic residues in the otherwise unrelated subtilisin and chymotrypsin families of enzymes [82]. 

All these approaches have been used to alter protein function, to increase the activity or solubility of proteins, or to adapt enzymes for industrial applications. The goal of artificial man-made proteins with tailor-made activities is, however, still far away and none of the currently existing approaches provides the ultimate solution to the directed evolution of proteins. Nevertheless, numerous examples of successfully altered and improved proteins clearly show the power of directed evolution for protein design. 

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