Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model
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Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model. / Tian, Pengfei; Lemaire, Adrien; Senechal, Fabien; Habrylo, Olivier; Antonietti, Viviane; Sonnet, Pascal; Lefebvre, Valerie; Marin, Frederikke Isa; Best, Robert B.; Pelloux, Jerome; Mercadante, Davide.
I: Angewandte Chemie International Edition, Bind 61, Nr. 50, e202202711, 2022, s. 1-8.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Design of a Protein with Improved Thermal Stability by an Evolution-Based Generative Model
AU - Tian, Pengfei
AU - Lemaire, Adrien
AU - Senechal, Fabien
AU - Habrylo, Olivier
AU - Antonietti, Viviane
AU - Sonnet, Pascal
AU - Lefebvre, Valerie
AU - Marin, Frederikke Isa
AU - Best, Robert B.
AU - Pelloux, Jerome
AU - Mercadante, Davide
PY - 2022
Y1 - 2022
N2 - Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.
AB - Efficient design of functional proteins with higher thermal stability remains challenging especially for highly diverse sequence variants. Considering the evolutionary pressure on protein folds, sequence design optimizing evolutionary fitness could help designing folds with higher stability. Using a generative evolution fitness model trained to capture variation patterns in natural sequences, we designed artificial sequences of a proteinaceous inhibitor of pectin methylesterase enzymes. These inhibitors have considerable industrial interest to avoid phase separation in fruit juice manufacturing or reduce methanol in distillates, averting chromatographic passages triggering unwanted aroma loss. Six out of seven designs with up to 30 % divergence to other inhibitor sequences are functional and two have improved thermal stability. This method can improve protein stability expanding functional protein sequence space, with traits valuable for industrial applications and scientific research.
KW - Coevolution
KW - Molecular Dynamics Simulations
KW - Monte Carlo Simulations
KW - Potts Models
KW - Protein Design
KW - PECTIN METHYLESTERASE
KW - SEQUENCE
KW - EPISTASIS
U2 - 10.1002/anie.202202711
DO - 10.1002/anie.202202711
M3 - Journal article
C2 - 36259321
VL - 61
SP - 1
EP - 8
JO - Angewandte Chemie International Edition
JF - Angewandte Chemie International Edition
SN - 1433-7851
IS - 50
M1 - e202202711
ER -
ID: 328020363