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PreprintCited by 6Enzyme Structure and FunctionProtein Structure and DynamicsPhotoreceptor and optogenetics research

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KINNTREX: A Neural Network Unveils Protein Mechanism from Time Resolved X-ray Crystallography

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Biener, Gabriel, Malla, Tek Narsingh, Schwander, Peter, Schmidt, Marius·2023·IUCrJ
DOI 10.1101/2023.10.06.561268PMC PMC11067743

Preprint — published as 10.1107/s2052252524002392 · Paper page

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Abstract

Here, a machine learning method based on a kinetically informed neural network (NN) is introduced. The proposed method is designed to analyze a time series of difference electron density (DED) maps from a time-resolved X-ray crystallographic experiment. The method is named KINNTREX (Kinetics Inspired NN for Time-Resolved X-ray Crystallography). To validate KINNTREX, multiple realistic scenarios were simulated with increasing level of complexity. For the simulations, time-resolved X-ray data was generated that mimic data collected from the photocycle of the photoactive yellow protein (PYP). KINNTREX only requires the number of intermediates and approximate relaxation times (both obtained from a singular valued decomposition) and does not require an assumption of a candidate mechanism. It successfully predicts a consistent chemical kinetic mechanism, together with difference electron density maps of the intermediates that appear during the reaction. These features make KINNTREX attractive for tackling a wide range of biomolecular questions. In addition, the versatility of KINNTREX can inspire more NN-based applications to time-resolved data from biological macromolecules obtained by other methods.

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Metadata

Authors
Biener, G., Malla, T. N., Schwander, P., & Schmidt, M.
Affiliations
University of Wisconsin–Milwaukee (US)
Corresponding author
Schmidt, Marius
ORCID
Venue
IUCrJ
Publisher
openRxiv
Published
2023-10-10
Volume
11
Issue
3
Pages
405-422
ISSN
2052-2525 (ISSN-L)
DOI
10.1101/2023.10.06.561268
PMC
PMC11067743
OpenAlex
W4395467417
Cited by
6
References
1
Citations by year
2026: 3 · 2025: 2
FWCI
0.49
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • IUCrJ (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Science Foundation (1231306)
  • Directorate for Biological Sciences (STC 1231306)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Enzyme Structure and Function
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Photoreceptor and optogenetics research
Keywords
time-resolved X-ray crystallography, reaction kinetics, kinetic intermediates, singular value decomposition, machine learning, artificial neural networks
MeSH terms
Machine Learning, Bacterial Proteins, Kinetics, Neural Networks, Computer, Crystallography, X-Ray, Photoreceptors, Microbial

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