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Numerical Techniques for Applications of Analytical Theories to Sequence-Dependent Phase Separations of Intrinsically Disordered Proteins

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Phase-Separated Biomolecular Condensates

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2563))

Abstract

Biomolecular condensates, physically underpinned to a significant extent by liquid–liquid phase separation (LLPS), are now widely recognized by numerous experimental studies to be of fundamental biological, biomedical, and biophysical importance. In the face of experimental discoveries, analytical formulations emerged as a powerful yet tractable tool in recent theoretical investigations of the role of LLPS in the assembly and dissociation of these condensates. The pertinent LLPS often involves, though not exclusively, intrinsically disordered proteins engaging in multivalent interactions that are governed by their amino acid sequences. For researchers interested in applying these theoretical methods, here we provide a practical guide to a set of computational techniques devised for extracting sequence-dependent LLPS properties from analytical formulations. The numerical procedures covered include those for the determination of spinodal and binodal phase boundaries from a general free energy function with examples based on the random phase approximation in polymer theory, construction of tie lines for multiple-component LLPS, and field-theoretic simulation of multiple-chain heteropolymeric systems using complex Langevin dynamics. Since a more accurate physical picture often requires comparing analytical theory against explicit-chain model predictions, a commonly utilized methodology for coarse-grained molecular dynamics simulations of sequence-specific LLPS is also briefly outlined.

Yi-Hsuan Lin, Jonas Wessén, and Tanmoy Pal contributed equally to this work.

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Acknowledgements

This work was supported by Canadian Institutes of Health Research grant NJT-155930 and Natural Sciences and Engineering Research Council of Canada grant RGPIN-2018-04351 as well as computational resources provided generously by Compute/Calcul Canada to H.S.C.

Y.-H.L., J.W., and T.P. contributed equally to this work.

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Authors and Affiliations

  1. Department of Biochemistry, University of Toronto, Toronto, ON, Canada

    Yi-Hsuan Lin

  2. Molecular Medicine, Hospital for Sick Children, Toronto, ON, Canada

    Yi-Hsuan Lin

  3. Department of Biochemistry, University of Toronto, Toronto, ON, Canada

    Jonas Wessén, Tanmoy Pal, Suman Das & Hue Sun Chan

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  1. Yi-Hsuan Lin
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  2. Jonas Wessén
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  3. Tanmoy Pal
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  4. Suman Das
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  5. Hue Sun Chan
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Correspondence to Hue Sun Chan .

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Editors and Affiliations

  1. Department of Chemistry, University of Illinois at Chicago, Chicago, IL, USA

    Huan-Xiang Zhou

  2. Department of Physics, University of Illinois at Chicago, Chicago, IL, USA

    Jan-Hendrik Spille

  3. Department of Physics, University at Buffalo, State University, Buffalo, NY, USA

    Priya R. Banerjee

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Lin, YH., Wessén, J., Pal, T., Das, S., Chan, H.S. (2023). Numerical Techniques for Applications of Analytical Theories to Sequence-Dependent Phase Separations of Intrinsically Disordered Proteins. In: Zhou, HX., Spille, JH., Banerjee, P.R. (eds) Phase-Separated Biomolecular Condensates. Methods in Molecular Biology, vol 2563. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2663-4_3

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