Imprint of evolution on protein structures

Guido Tiana, Boris E. Shakhnovicht, Nikolay V. Dokholyan, Eugene I. Shakhnovich

Research output: Contribution to journalArticle

44 Scopus citations

Abstract

We attempt to understand the evolutionary origin of protein folds by simulating their divergent evolution with a three-dimensional lattice model. Starting from an initial seed lattice structure, evolution of model proteins progresses by sequence duplication and subsequent point mutations. A new gene's ability to fold into a stable and unique structure is tested each time through direct kinetic folding simulations. Where possible, the algorithm accepts the new sequence and structure and thus a "new protein structure" is born. During the course of each run, this model evolutionary algorithm provides several thousand new proteins with diverse structures. Analysis of evolved structures shows that later evolved structures are more designable than seed structures as judged by recently developed structural determinant of protein designability, as well as direct estimate of designability for selected structures by thermodynamic sampling of their sequence space. We test the significance of this trend predicted on lattice models on real proteins and show that protein domains that are found in eukaryotic organisms only feature statistically significant higher design-ability than their prokaryotic counterparts. These results present a fundamental view on protein evolution highlighting the relative roles of structural selection and evolutionary dynamics on genesis of modern proteins.

Original languageEnglish (US)
Pages (from-to)2846-2851
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume101
Issue number9
DOIs
StatePublished - Mar 2 2004

All Science Journal Classification (ASJC) codes

  • General

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