Patterns of coevolving amino acids unveil structural and dynamical domains.

Abstract:

:Patterns of interacting amino acids are so preserved within protein families that the sole analysis of evolutionary comutations can identify 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? To address this question, we introduce here a general coevolutionary coupling analysis strategy and apply it to a curated sequence database of hundreds of protein families. For most families, the sequence-based method partitions amino acids into a few clusters. When viewed in the context of the native structure, these clusters have the signature characteristics of viable protein domains: They are spatially separated but individually compact. They have a direct functional bearing too, as shown for various reference cases. We conclude that even large-scale structural and functionally related properties can be recovered from inference methods applied to evolutionary-related sequences. The method introduced here is available as a software package and web server (spectrus.sissa.it/spectrus-evo_webserver).

authors

Granata D,Ponzoni L,Micheletti C,Carnevale V

doi

10.1073/pnas.1712021114

subject

Has Abstract

pub_date

2017-12-12 00:00:00

pages

E10612-E10621

issue

50

eissn

0027-8424

issn

1091-6490

pii

1712021114

journal_volume

114

pub_type

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