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Differentiating Unimodal and Multimodal Distributions in Pulsed Dipolar Spectroscopy Using Wavelet Transforms

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Abstract

Site-directed spin labeling has enabled protein structure determination using electron spin resonance pulsed dipolar spectroscopy (PDS). Small details in a distance distribution can be key to understanding important protein structure–function relationships. A major challenge has been to differentiate unimodal and overlapped multimodal distance distributions. They often yield similar distributions and dipolar signals. Current model-free distance reconstruction techniques, such as Srivastava-Freed singular value decomposition and Tikhonov regularization, can suppress these small features in uncertainty and/or error bounds, despite being present. In this work, we demonstrate that continuous wavelet transform (CWT) can distinguish PDS signals from unimodal and multimodal distance distributions. We show that periodicity in CWT representation reflects unimodal distributions, which is masked for multimodal cases. This work is meant as a precursor to a cross-validation technique, which could indicate the modality of the distance distribution.

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Data and the code used in this work have been stored in the public github repository (https://github.com/Signal-Science-Lab).

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Funding

This research was funded by the NSF Grant No. 2044599 and the National Institute of General Medical Sciences/National Institutes of Health under Grant No. R24GM146107 and R35GM148272.

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Authors and Affiliations

  1. Department of Chemistry and Chemical Biology, Cornell University, Baker Laboratory, Ithaca, NY, 14853, USA

    Aritro Sinha Roy, Jack H. Freed & Madhur Srivastava

  2. National Biomedical Resource for Advanced ESR Spectroscopy, Cornell University, Baker Laboratory, Ithaca, NY, 14853, USA

    Aritro Sinha Roy, Jack H. Freed & Madhur Srivastava

  3. Cornell Atkinson Center for Sustainability, Cornell University, 340 Tower Road, Ithaca, NY, 14853, USA

    Madhur Srivastava

Authors
  1. Aritro Sinha Roy
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  2. Jack H. Freed
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  3. Madhur Srivastava
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Contributions

Conceptualization, ASR, JHF, and MS; methodology, ASR and MS; formal analysis, ASR; writing—original draft preparation, ASR; writing—review and editing, JHF and MS; visualization, ASR; supervision, MS; project administration, MS; funding acquisition, JHF and MS. All authors have read and agreed to the published version of the manuscript.

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Correspondence to Madhur Srivastava.

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Appendix A: DEERLab Script

Appendix A: DEERLab Script

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Sinha Roy, A., Freed, J.H. & Srivastava, M. Differentiating Unimodal and Multimodal Distributions in Pulsed Dipolar Spectroscopy Using Wavelet Transforms. Appl Magn Reson 55, 219–237 (2024). https://doi.org/10.1007/s00723-023-01616-w

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  • DOI: https://doi.org/10.1007/s00723-023-01616-w

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