Induced fit, conformational selection and independent dynamic segments: an extended view of binding events

By Peter Csermely, Robin Palotai, Ruth Nussinov. TIBS -Trends in Biochemical Sciences. Regular ed, 2010

801 citations recorded by the source corpus.

Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here we describe an extended conformational selection model which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein (‘discrete breathers’) can govern conformational transitions and allosteric propagation that accompany binding processes, and as such might be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/6c3d6dd792643330bd122736ce61ef3153005ec9

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Citations in the corpus

How does a small molecule bind at a cryptic binding site? (2021, background): “Many binding processes, however, may have a hybrid character, with some native ligand-protein interactions first forming as an “anchor” (as in conformational selection), and “latch” interactions subsequently forming in ways consistent with an induced-fit process.(39)”
A Unified Conformational Selection and Induced Fit Approach to Protein-Peptide Docking (2013, positive): “In recent years, a shift toward a reconciliation of both models can be observed where conformational selection and induced fit may be in fact co-existing [42–45].”
The roles of conditional disorder in redox proteins (2013, background): “In the conformational selection model, ligand binding shifts the structural equilibrium toward a more stable conformation [41,42].”
Insights into Protein–Ligand Interactions: Mechanisms, Models, and Methods (2016, background): “Three different models, the “lock-and-key” [50], “induced fit” [51] and “conformational selection” [24,26,52,53], have been proposed to explain the protein–ligand binding mechanisms.”
Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review (2012, background): “…the mechanism of allosteric changes gained much attention in the last century (Fischer, 1894; Koshland, 1958; Straub & Szabolcsi, 1964; Závodszky et al., 1966; Tsai et al., 1999; Goodey & Benkovic, 2008; Csermely et al., 2010; Szilágyi et al., in press), but have not been completely elucidated yet.”
Pre‐ and post‐docking sampling of conformational changes using ClustENM and HADDOCK for protein‐protein and protein‐DNA systems (2019, background): “8,9 A study on a set of complexes with rather limited conformational changes 10 has addressed the ability of current computational techniques to capture the conformational changes upon binding and concluded that current “ conformational selection ” methods can capture 22% of unbound-bound…”