The induced fit model is the correct representation of enzyme-substrate complementarity
While the classic induced-fit model remains a foundational concept in enzymology supported by numerous studies on substrate-driven conformational changes, modern biophysical research demonstrates that many enzymes actually utilize a combination of conformational selection and induced-fit mechanisms.
The claim states that the induced fit model is the correct representation of enzyme-substrate complementarity. Several papers support the occurrence and importance of induced-fit conformational changes in various enzymes (e.g., papers 0, 1, 7, 8, 11). However, modern structural biology and kinetics show that enzyme binding often involves both conformational selection and induced fit acting in concert or as part of a dynamic ensemble (e.g., papers 4, 9, 10). Because the field views enzyme-substrate complementarity as a more nuanced combination of mechanisms rather than a single correct induced-fit representation, the verdict is CONTESTED.
C. Lai, Huei-Jiun Lic, Weixuan Yu, S. Shah, G. Bommineni, Victoria Perrone, M. García-Díaz, P. Tonge, Carlos Simmerling. Rational modulation of the induced-fit conformational change for slow-onset inhibition in M. tuberculosis InhA. 2015. https://doi.org/10.1021/acs.biochem.5b00284
This study validates the induced-fit mechanistic hypothesis involving substrate-binding loop conformational changes.
Nussinov R, Regev C, Jang H. Leveraging conformational ensembles in allosteric drug discovery.. 2026. https://doi.org/10.1016/j.tips.2026.01.006
This paper notes that the traditional strict induced-fit model has limitations and that proteins actually exist as dynamic conformational ensembles.
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Ingolf Harden, F. Neese, G. Bistoni. An induced-fit model for asymmetric organocatalytic reactions: a case study of the activation of olefins via chiral Brønsted acid catalysts. 2022. https://doi.org/10.1039/d2sc02274e
This work describes catalyst-substrate interactions using a dispersion-driven induced-fit model.
Hegazy R, Richard JP. The Role of Protein Side Chains in Enzyme-Activating Conformational Changes: Lessons from Studies on Variant Enzymes.. 2025. https://doi.org/10.1021/acs.chemrev.5c00572
This paper highlights how substrate-driven protein conformational changes achieve optimal transition-state stabilization, consistent with induced-fit mechanisms.
S. R. Varikasuvu, Lavanya Ranvee, Saurabh Varshney, Himel Mondal. Pen and palm model to envision the coexistence of induced-fit and substrate-strain theories of enzyme action.. 2024. https://doi.org/10.1152/advan.00100.2024
This educational model illustrates how the induced-fit theory explains enzyme-substrate engagement.
Serdal Kirmizialtin, R. Elber, K. Johnson. Antlion Strategy for Enzyme Specificity. 2012. https://doi.org/10.1016/J.BPJ.2011.11.1502
This research demonstrates that substrate-induced conformational changes govern enzyme specificity.
C. Loomis, Michelle Redhair, Sang-Choul Im, Emily E. Scott. Redox partner adrenodoxin induces substrate binding to steroidogenic cytochrome P450 11B2 and 11A1 by promoting a conformational change. 2025. https://doi.org/10.1016/j.jbc.2025.110792
This study finds that substrate binding does not rely solely on induced fit, but rather on combined or branched models involving conformational selection steps.
Yanjun Zhang, Xule Zhao, Yuxin Tian, Shun Zhang, Feng Fan, Xiafei Hao. GID4 Recognition of Pro/N-Degron Peptides: Conformational Selection and Induced Fit.. 2025. https://doi.org/10.1016/j.bpj.2025.05.016
This research shows that substrate recognition follows a combined mechanism of both conformational selection and induced fit rather than pure induced fit.
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