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Volume 26, Issue 3
  • ISSN: 1389-2037
  • E-ISSN: 1875-5550

Abstract

Introduction

The Q108P pathological variant of the mitochondrial Coiled-Coil-Helix-Coiled-Coil-Helix Domain-Containing Protein 10 (CHCHD10) has been implicated in amyotrophic lateral sclerosis (ALS). Both the wild-type and CHCHD10Q108P proteins exhibit intrinsically disordered regions, posing challenges for structural studies with conventional experimental tools.

Methods

This study presents the foundational characterization of the structural features of CHCHD10Q108P and compares them with those of the wild-type counterpart. We conducted multiple run molecular dynamics simulations and bioinformatics analyses.

Results

Our findings reveal distinct differences in structural properties, free energy surfaces, and the outputs of principal component analysis between these two proteins. These results contribute significantly to the comprehension of CHCHD10 and its Q108P variant in terms of pathology, biochemistry, and structural biology.

Conclusion

The reported structural properties hold promise for informing the development of more effective treatments for ALS.

© 2025 Bentham Science Publishers
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2024-10-23
2025-04-28

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Effects of the Amyotrophic Lateral Sclerosis-related Q108P Mutation on the Structural Ensemble Characteristics of CHCHD10
Curr. Protein Pept. Sci. 26, 201 (2025); https://doi.org/10.2174/0113892037335036241007043530
/content/journals/cpps/10.2174/0113892037335036241007043530
/content/journals/cpps/10.2174/0113892037335036241007043530
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Supplements

Data obtained from run 1, run 2, and run 3 MD simulations are presented in the Supporting Information section. We present the root mean square deviations, secondary structure elements, root mean square fluctuations, free energy surfaces, tertiary structure properties, Ramachandran plots, and the principal component analysis results. Supplementary material is available on the publisher’s web site along with the published article.

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  • Article Type:     Research Article
Keyword(s): amyotrophic lateral sclerosis; bioinformatics; CHCHD10; genetics; multiple run molecular dynamics simulations; Q108P; structural properties

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