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Conformational Ensembles from Experimental Data
and Computer Simulations
Poster Abstracts
69
36-POS
Board 36
From Sequence to Function: Coevolving Amino Acids Encode Structural and Dynamical
Domains
Daniele Granata
1,2
, Luca Ponzoni
3
, Kresten Lindorff-Larsen
1
, Cristian Micheletti
3
, Vincenzo
Carnevale
2
.
1
University of Copenhagen, Kobenhavn, Denmark,
2
Temple University, Philadelphia, PA, USA,
3
SISSA, Trieste, Italy.
Amino acids interactions within protein families are so optimized that the sole analysis of
evolutionary co-mutations can pinpoint pairs of contacting residues. It is also known that
evolution conserves functional dynamics, i.e., the concerted motion or displacement of large
protein regions or domains. Is it, therefore, possible to use a pure sequence-based analysis to
identify these dynamical domains? We introduce a general co-evolutionary coupling analysis
strategy and apply it to a curated sequence database of 800 protein families. As soon as few
hundreds of sequence are available for the coupling inference, the sequence-based method
partitions amino acids into clusters spatially separated but individually compact, when
represented on the relative native structure. Remarkably, these "Evolutionary Domains" are also
highly correlated with proteins dynamical domains, encoding their structural dynamics. Finally
we discuss relevant applications to comparative analysis within ion channels family and to the
identification of allosteric communication between domains in specific enzymes.