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Trends Biochem Sci. 2006 Jul;31(7):374-82.

Bayesian shadows of molecular mechanisms cast in the light of evolution.

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1
Cold Spring Harbor Laboratory, 1 Bungtown Road, PO Box 100, Cold Spring Harbor, NY 11724, USA. neuwald@cshl.edu

Abstract

A great many carefully designed experiments will be required to fully understand biological mechanisms in atomic detail. A complementary approach is to use powerful statistical procedures to rapidly test numerous scientific hypotheses using vast numbers of protein sequences--the cell's own blueprints for specifying biological mechanisms. Bayesian inference of the evolutionary constraints imposed on functionally divergent proteins can reveal key components of the molecular machinery and thereby suggest likely mechanisms to test experimentally. This approach is demonstrated by considering how DNA polymerase clamp-loader AAA+ ATPases couple DNA recognition to ATP hydrolysis and clamp loading.

PMID:
16766187
DOI:
10.1016/j.tibs.2006.05.002
[Indexed for MEDLINE]
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