---
_id: '11448'
abstract:
- lang: eng
text: Studies of protein fitness landscapes reveal biophysical constraints guiding
protein evolution and empower prediction of functional proteins. However, generalisation
of these findings is limited due to scarceness of systematic data on fitness landscapes
of proteins with a defined evolutionary relationship. We characterized the fitness
peaks of four orthologous fluorescent proteins with a broad range of sequence
divergence. While two of the four studied fitness peaks were sharp, the other
two were considerably flatter, being almost entirely free of epistatic interactions.
Mutationally robust proteins, characterized by a flat fitness peak, were not optimal
templates for machine-learning-driven protein design – instead, predictions were
more accurate for fragile proteins with epistatic landscapes. Our work paves insights
for practical application of fitness landscape heterogeneity in protein engineering.
acknowledged_ssus:
- _id: LifeSc
- _id: Bio
acknowledgement: "We thank Ondřej Draganov, Rodrigo Redondo, Bor Kavčič, Mia Juračić
and Andrea Pauli for discussion and technical advice. We thank Anita Testa Salmazo
for advice on resin protein purification, Dmitry Bolotin and the Milaboratory (milaboratory.com)
for access to computing and storage infrastructure, and Josef Houser and Eva Fujdiarova
for technical assistance and data interpretation. Core facility Biomolecular Interactions
and Crystallization of CEITEC Masaryk University is gratefully acknowledged for
the obtaining of the scientific data presented in this paper. This research was
supported by the Scientific Service Units (SSU) of IST-Austria\r\nthrough resources
provided by the Bioimaging Facility (BIF), and the Life Science Facility (LSF).
MiSeq and HiSeq NGS sequencing was performed by the Next Generation Sequencing Facility
at Vienna BioCenter Core Facilities (VBCF), member of the Vienna BioCenter (VBC),
Austria. FACS was performed at the BioOptics Facility of the Institute of Molecular
Pathology (IMP), Austria. We also thank the Biomolecular Crystallography Facility
in the Vanderbilt University Center for Structural Biology. We are grateful to Joel
M Harp for help with X-ray data collection. This work was supported by the ERC Consolidator
grant to FAK (771209—CharFL). KSS acknowledges support by President’s Grant МК–5405.2021.1.4,
the Imperial College Research Fellowship and the MRC London Institute of Medical
Sciences (UKRI MC-A658-5QEA0).\r\nAF is supported by the Marie Skłodowska-Curie
Fellowship (H2020-MSCA-IF-2019, Grant Agreement No. 898203, Project acronym \"FLINDIP\").
Experiments were partially carried out using equipment provided by the Institute
of Bioorganic Chemistry of the Russian Academy of Sciences Сore Facility (CKP IBCH).
This work was supported by a Russian Science Foundation grant 19-74-10102.This project
has received funding from the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie Grant Agreement No. 665,385."
article_number: '75842'
article_processing_charge: No
article_type: original
author:
- first_name: Louisa
full_name: Gonzalez Somermeyer, Louisa
id: 4720D23C-F248-11E8-B48F-1D18A9856A87
last_name: Gonzalez Somermeyer
orcid: 0000-0001-9139-5383
- first_name: Aubin
full_name: Fleiss, Aubin
last_name: Fleiss
- first_name: Alexander S
full_name: Mishin, Alexander S
last_name: Mishin
- first_name: Nina G
full_name: Bozhanova, Nina G
last_name: Bozhanova
- first_name: Anna A
full_name: Igolkina, Anna A
last_name: Igolkina
- first_name: Jens
full_name: Meiler, Jens
last_name: Meiler
- first_name: Maria-Elisenda
full_name: Alaball Pujol, Maria-Elisenda
last_name: Alaball Pujol
- first_name: Ekaterina V
full_name: Putintseva, Ekaterina V
last_name: Putintseva
- first_name: Karen S
full_name: Sarkisyan, Karen S
last_name: Sarkisyan
- first_name: Fyodor
full_name: Kondrashov, Fyodor
id: 44FDEF62-F248-11E8-B48F-1D18A9856A87
last_name: Kondrashov
orcid: 0000-0001-8243-4694
citation:
ama: Gonzalez Somermeyer L, Fleiss A, Mishin AS, et al. Heterogeneity of the GFP
fitness landscape and data-driven protein design. eLife. 2022;11. doi:10.7554/elife.75842
apa: Gonzalez Somermeyer, L., Fleiss, A., Mishin, A. S., Bozhanova, N. G., Igolkina,
A. A., Meiler, J., … Kondrashov, F. (2022). Heterogeneity of the GFP fitness landscape
and data-driven protein design. ELife. eLife Sciences Publications. https://doi.org/10.7554/elife.75842
chicago: Gonzalez Somermeyer, Louisa, Aubin Fleiss, Alexander S Mishin, Nina G Bozhanova,
Anna A Igolkina, Jens Meiler, Maria-Elisenda Alaball Pujol, Ekaterina V Putintseva,
Karen S Sarkisyan, and Fyodor Kondrashov. “Heterogeneity of the GFP Fitness Landscape
and Data-Driven Protein Design.” ELife. eLife Sciences Publications, 2022.
https://doi.org/10.7554/elife.75842.
ieee: L. Gonzalez Somermeyer et al., “Heterogeneity of the GFP fitness landscape
and data-driven protein design,” eLife, vol. 11. eLife Sciences Publications,
2022.
ista: Gonzalez Somermeyer L, Fleiss A, Mishin AS, Bozhanova NG, Igolkina AA, Meiler
J, Alaball Pujol M-E, Putintseva EV, Sarkisyan KS, Kondrashov F. 2022. Heterogeneity
of the GFP fitness landscape and data-driven protein design. eLife. 11, 75842.
mla: Gonzalez Somermeyer, Louisa, et al. “Heterogeneity of the GFP Fitness Landscape
and Data-Driven Protein Design.” ELife, vol. 11, 75842, eLife Sciences
Publications, 2022, doi:10.7554/elife.75842.
short: L. Gonzalez Somermeyer, A. Fleiss, A.S. Mishin, N.G. Bozhanova, A.A. Igolkina,
J. Meiler, M.-E. Alaball Pujol, E.V. Putintseva, K.S. Sarkisyan, F. Kondrashov,
ELife 11 (2022).
date_created: 2022-06-18T09:06:59Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2023-08-03T07:20:15Z
day: '05'
ddc:
- '570'
department:
- _id: GradSch
- _id: FyKo
doi: 10.7554/elife.75842
ec_funded: 1
external_id:
isi:
- '000799197200001'
file:
- access_level: open_access
checksum: 7573c28f44028ab0cc81faef30039e44
content_type: application/pdf
creator: dernst
date_created: 2022-06-20T07:44:19Z
date_updated: 2022-06-20T07:44:19Z
file_id: '11454'
file_name: 2022_eLife_Somermeyer.pdf
file_size: 5297213
relation: main_file
success: 1
file_date_updated: 2022-06-20T07:44:19Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
keyword:
- General Immunology and Microbiology
- General Biochemistry
- Genetics and Molecular Biology
- General Medicine
- General Neuroscience
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '05'
oa: 1
oa_version: Published Version
project:
- _id: 26580278-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '771209'
name: Characterizing the fitness landscape on population and global scales
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: eLife
publication_identifier:
issn:
- 2050-084X
publication_status: published
publisher: eLife Sciences Publications
quality_controlled: '1'
scopus_import: '1'
status: public
title: Heterogeneity of the GFP fitness landscape and data-driven protein design
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2022'
...