ArticlePLoS computational biology2010
Scalable rule-based modelling of allosteric proteins and biochemical networks.
Article in PLoS computational biology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed.
- Cooperation of transposable elements to endow global networks of initiators of hybrid assembly pathways of endogenous multiprotein complexes.Frontiers in cellular and infection microbiology · 2026Article
- Mechanistic model of MAPK signaling reveals how allostery and rewiring contribute to drug resistance.Molecular systems biology · 2023Article
- A Practical Guide for the Efficient Formulation and Calibration of Large, Energy- and Rule-Based Models of Cellular Signal Transduction.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Article
- Analysing and simulating energy-based models in biology using BondGraphTools.The European physical journal. E, Soft matter · 2021Article
- Modular assembly of dynamic models in systems biology.PLoS computational biology · 2021Article
- A systems-biology approach to molecular machines: Exploration of alternative transporter mechanisms.PLoS computational biology · 2020Article
- Bivalent Ligands for Protein Degradation in Drug Discovery.Computational and structural biotechnology journal · 2019Review
- φ-evo: A program to evolve phenotypic models of biological networks.PLoS computational biology · 2018Article
- Cooperative binding mitigates the high-dose hook effect.BMC systems biology · 2017Article
- Extending rule-based methods to model molecular geometry and 3D model resolution.BMC systems biology · 2016Article
- Enzyme Sequestration as a Tuning Point in Controlling Response Dynamics of Signalling Networks.PLoS computational biology · 2016Article
- BioJazz: in silico evolution of cellular networks with unbounded complexity using rule-based modeling.Nucleic acids research · 2015Article
- Modeling for (physical) biologists: an introduction to the rule-based approach.Physical biology · 2015Review
- Analytical reduction of combinatorial complexity arising from multiple protein modification sites.Journal of the Royal Society, Interface · 2015Article
- Retour aux sources: defining the structural basis of glutamate receptor activation.The Journal of physiology · 2015Review
- Multi-state modeling of biomolecules.PLoS computational biology · 2014Article
- A rule-based kinetic model of RNA polymerase II C-terminal domain phosphorylation.Journal of the Royal Society, Interface · 2013Article
- Systems biophysics of gene expression.Biophysical journal · 2013Review
- A comprehensive mathematical model for three-body binding equilibria.Journal of the American Chemical Society · 2013Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Much of the complexity of biochemical networks comes from the information-processing abilities of allosteric proteins, be they receptors, ion-channels, signalling molecules or transcription factors. An allosteric protein can be uniquely regulated by each combination of input molecules that it binds. This "regulatory complexity" causes a combinatorial increase in the number of parameters required to fit experimental data as the number of protein interactions increases. It therefore challenges the creation, updating, and re-use of biochemical models. Here, we propose a rule-based modelling framework that exploits the intrinsic modularity of protein structure to address regulatory complexity. Rather than treating proteins as "black boxes", we model their hierarchical structure and, as conformational changes, internal dynamics. By modelling the regulation of allosteric proteins through these conformational changes, we often decrease the number of parameters required to fit data, and so reduce over-fitting and improve the predictive power of a model. Our method is thermodynamically grounded, imposes detailed balance, and also includes molecular cross-talk and the background activity of enzymes. We use our Allosteric Network Compiler to examine how allostery can facilitate macromolecular assembly and how competitive ligands can change the observed cooperativity of an allosteric protein. We also develop a parsimonious model of G protein-coupled receptors that explains functional selectivity and can predict the rank order of potency of agonists acting through a receptor. Our methodology should provide a basis for scalable, modular and executable modelling of biochemical networks in systems and synthetic biology.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.