Thursday, September 19, 2013

diffusion through conformational space?

Protein evolution as diffusion through conformational space?

Shouldn't it be diffusion through typographical space?

Another thing:  If it is an easy thing to make a protein for any particular effect, why isn't it exceptionally easy to make a protein that really gums up the works?  either ties itself into a useless little knot or turns into something that binds with all sorts of things it shouldn't and kills its organism (slowly or quickly)?

But then again maybe it isn't that easy:
The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions1234. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: ~98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, ~3.5×109yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.

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