TY - JOUR
T1 - Correlated Evolution of Low-Frequency Vibrations and Function in Enzymes
AU - Modi, Tushar
AU - Campitelli, Paul
AU - Heyden, Matthias
AU - Ozkan, S. Banu
N1 - Funding Information:
The authors gratefully acknowledge computational resources provided by Research Computing at Arizona State University. S.B.O. is supported by the National Science Foundation Division of Molecular and Cellular Biosciences (MCB-1715591) and the Gordon and Betty Moore Foundation Award #8415. M.H. is grateful for financial support by the National Science Foundation (CHE-2154834).
Publisher Copyright:
© 2023 American Chemical Society.
PY - 2023/1/26
Y1 - 2023/1/26
N2 - Previous studies of the flexibility of ancestral proteins suggest that proteins evolve their function by altering their native state ensemble. Here, we propose a more direct method to analyze such changes during protein evolution by comparing thermally activated vibrations at frequencies below 6 THz, which report on the dynamics of collective protein modes. We analyzed the backbone vibrational density of states of ancestral and extant β-lactamases and thioredoxins and observed marked changes in the vibrational spectrum in response to evolution. Coupled with previously observed changes in protein flexibility, the observed shifts of vibrational mode densities suggest that protein dynamics and dynamical allostery are critical factors for the evolution of enzymes with specialized catalytic and biophysical properties.
AB - Previous studies of the flexibility of ancestral proteins suggest that proteins evolve their function by altering their native state ensemble. Here, we propose a more direct method to analyze such changes during protein evolution by comparing thermally activated vibrations at frequencies below 6 THz, which report on the dynamics of collective protein modes. We analyzed the backbone vibrational density of states of ancestral and extant β-lactamases and thioredoxins and observed marked changes in the vibrational spectrum in response to evolution. Coupled with previously observed changes in protein flexibility, the observed shifts of vibrational mode densities suggest that protein dynamics and dynamical allostery are critical factors for the evolution of enzymes with specialized catalytic and biophysical properties.
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U2 - 10.1021/acs.jpcb.2c05983
DO - 10.1021/acs.jpcb.2c05983
M3 - Article
C2 - 36633931
AN - SCOPUS:85146386627
SN - 1520-6106
VL - 127
SP - 616
EP - 622
JO - Journal of Physical Chemistry B
JF - Journal of Physical Chemistry B
IS - 3
ER -