Imprint of evolution on protein structures

G. Tiana, B. E. Shakhnovich, N. V. Dokholyan, E. I. Shakhnovich
2004 Proceedings of the National Academy of Sciences of the United States of America  
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
more » ... ew 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 designability 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.
doi:10.1073/pnas.0306638101 pmid:14970345 pmcid:PMC365708 fatcat:kyvi5xt6jbbhlj52opmglufahy