Issue 4, 2023

Straightforward model construction and analysis of multicomponent biomolecular systems in equilibrium

Abstract

Mathematical modelling of molecular systems can be extremely helpful in elucidating complex phenomena in (bio)chemistry. However, equilibrium conditions in systems consisting of more than two components, such as for molecular glues bound to two proteins, can typically not be analytically determined without assumptions and (semi-)numerical models are not trivial to derive by the non-expert. Here we present a framework for equilibrium models, geared towards molecular glues and other contemporary multicomponent chemical biology challenges. The framework utilizes a general derivation method capable of generating custom mass-balance models for equilibrium conditions of complex molecular systems, based on the simple, reversible biomolecular reactions describing these systems. Several chemical biology concepts are revisited via the framework to demonstrate the simplicity, generality and validity of the approach. The ease of use of the framework and the ability to both analyze systems and gain additional insights in the underlying parameters driving equilibria formation strongly aids the analysis and understanding of biomolecular systems. New directions for research and analysis are brought forward based on the model formation and system and parameter analysis. This conceptual framework severely reduces the time and expertise requirements which currently impede the broad integration of such valuable equilibrium models into molecular glue development and chemical biology research.

Graphical abstract: Straightforward model construction and analysis of multicomponent biomolecular systems in equilibrium

Supplementary files

Article information

Article type
Paper
Submitted
04 okt 2022
Accepted
17 jan 2023
First published
18 jan 2023
This article is Open Access
Creative Commons BY license

RSC Chem. Biol., 2023,4, 252-260

Straightforward model construction and analysis of multicomponent biomolecular systems in equilibrium

N. H. J. Geertjens, P. J. de Vink, T. Wezeman, A. J. Markvoort and L. Brunsveld, RSC Chem. Biol., 2023, 4, 252 DOI: 10.1039/D2CB00211F

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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