---
_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. <i>eLife</i>. 2022;11. doi:<a
    href="https://doi.org/10.7554/elife.75842">10.7554/elife.75842</a>
  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. <i>ELife</i>. eLife Sciences Publications. <a
    href="https://doi.org/10.7554/elife.75842">https://doi.org/10.7554/elife.75842</a>
  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.” <i>ELife</i>. eLife Sciences Publications, 2022.
    <a href="https://doi.org/10.7554/elife.75842">https://doi.org/10.7554/elife.75842</a>.
  ieee: L. Gonzalez Somermeyer <i>et al.</i>, “Heterogeneity of the GFP fitness landscape
    and data-driven protein design,” <i>eLife</i>, 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.” <i>ELife</i>, vol. 11, 75842, eLife Sciences
    Publications, 2022, doi:<a href="https://doi.org/10.7554/elife.75842">10.7554/elife.75842</a>.
  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).
corr_author: '1'
date_created: 2022-06-18T09:06:59Z
date_published: 2022-05-05T00:00:00Z
date_updated: 2026-10-02T11:21:40Z
day: '05'
ddc:
- '570'
department:
- _id: GradSch
- _id: FyKo
doi: 10.7554/elife.75842
ec_funded: 1
external_id:
  isi:
  - '000799197200001'
  pmid:
  - '35510622'
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
fulldoi: https://doi.org/10.7554/elife.75842
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
month: '05'
oa: 1
oa_version: Published Version
pmid: 1
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'
related_material:
  link:
  - relation: software
    url: https://github.com/aequorea238/Orthologous_GFP_Fitness_Peaks
  record:
  - id: '17850'
    relation: dissertation_contains
    status: public
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2022'
...