Bayesian shadows of molecular mechanisms cast in the light of evolution.
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.
Neuwald
Andrew F
AF
Cold Spring Harbor Laboratory, 1 Bungtown Road, PO Box 100, Cold Spring Harbor, NY 11724, USA. neuwald@cshl.edu
D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D001499:Bayes Theorem; D004258:DNA Polymerase III / Q000502:physiology*; D019143:Evolution, Molecular; D008958:Models, Molecular; D008969:Molecular Sequence Data; D051818:Replication Protein C / Q000502:physiology; D016415:Sequence Alignment
D000255:Adenosine Triphosphate; C065639:DNA polymerase A; D004258:DNA Polymerase III; D000251:Adenosine Triphosphatases; D051818:Replication Protein C