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bioRxiv · 10.1101/2024.03.25.586698

COCONUT: An analysis of coiled-coil regions in proteins

Soni, N.·Madhusudhan, M. S.
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Abstract

MotivationThe molecular rules determine the strength and orientation (parallel or antiparallel) of interacting coiled-coil helices in protein-protein interactions. Interpreting these rules is crucial for identifying novel protein-protein interactions, designing competitive binders, and constructing large assemblies containing coiled-coil domains. This study establishes the molecular principles that dictate the strength and orientation of coiled-coil interactions, providing insights relevant to these applications. ResultsWe examined how hydrophobic contacts determine structural specificity within coiled-coil dimers. Our analysis revealed that the hydrophobic core densities differ between parallel and antiparallel dimer confirmations, highlighting their importance in stabilizing different structural arrangements. We developed COiled-COil aNalysis UTility (COCONUT), a computational platform with machine learning models, validated for predictive capabilities in various applications. Using COCONUTs pipeline for coiled-coil analysis and modeling, we predicted the orientation of substitution-sensitive coiled-coil dimer, identified residue pairings in non-canonical coiled-coil heterodimer, and constructed n-stranded coiled-coil model. These results demonstrate COCONUTs utility as a computational framework for interpreting and modeling coiled-coil structures. Availability and implementationCOCONUT is an open-source and free Python package available here https://github.com/neeleshsoni21/COCONUT. The documentation is available in the source code and here: https://neeleshsoni21.github.io/COCONUT/

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Soni, N., Madhusudhan, M. S.. 2024-03-29. COCONUT: An analysis of coiled-coil regions in proteins. https://doi.org/10.1101/2024.03.25.586698

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