RT Journal Article
T1 A Generative Angular Model of Protein Structure Evolution
A1 Golden, Michael
A1 García Portugués, Eduardo
A1 Sørensen, Michael
A1 Mardia, Kanti V.
A1 Hamelryck, Thomas
A1 Hein, Jotun
K1 Evolution
K1 Protein structure
K1 Probabilistic model
K1 Directional statistics
AB Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a generative, evolutionary model of protein structure and sequence that is valid on a local length scale. The model concerns the local dependencies between sequence and structure evolution in a pair of homologous proteins. The evolutionary trajectory between the two structures in the protein pair is treated as a random walk in dihedral angle space, which is modeled using a novel angular diffusion process on the two-dimensional torus. Coupling sequence and structure evolution in our model allows for modeling both “smooth” conformational changes and “catastrophic” conformational jumps, conditioned on the amino acid changes. The model has interpretable parameters and is comparatively more realistic than previous stochastic models, providing new insights into the relationship between sequence and structure evolution. For example, using the trained model we were able to identify an apparent sequence–structure evolutionary motif present in a large number of homologous protein pairs. The generative nature of our model enables us to evaluate its validity and its ability to simulate aspects of protein evolution conditioned on an amino acid sequence, a related amino acid sequence, a related structure or any combination thereof
PB Oxford University Press
SN 0737-4038
YR 2017
FD 2017-04-27
LK http://hdl.handle.net/10347/18400
UL http://hdl.handle.net/10347/18400
LA eng
NO Michael Golden, Eduardo García-Portugués, Michael Sørensen, Kanti V. Mardia, Thomas Hamelryck, Jotun Hein; A Generative Angular Model of Protein Structure Evolution, Molecular Biology and Evolution, Volume 34, Issue 8, 1 August 2017, Pages 2085–2100, https://doi.org/10.1093/molbev/msx137
NO The authors acknowledge funding from the University of Copenhagen 2016 Excellence Programme for Interdisciplinary Research (UCPH2016-DSIN). The second author acknowledges support from project MTM2016-76969-P from the Spanish Ministry of Economy and Competitiveness and ERDF
DS Minerva
RD 25 abr 2026