A Computational Study of Competing Conformational Selection and Induced Fit in an Abiotic System

2021 ◽  
Author(s):  
Jovica D. Badjic ◽  
Christopher M Hadad ◽  
Remy F Lalisse ◽  
Radoslav Z Pavlović
Keyword(s):  
Computational Study ◽  
Elastic Band ◽  
Induced Fit ◽  
Conformational Selection

Host-guest complexations can be described by two competing mechanisms, conformational selection (CS) and induced fit (IF). In this work, we used a combination of nudged elastic band (NEB), adaptive steered...

Association/dissociation Mechanisms of Intrinsically Disordered Region of Protein Beyond Conformational Selection and Induced Fit

2019 ◽  
Author(s):  
Duy Phuoc Tran ◽  
Akio Kitao
Keyword(s):  
Free Energy ◽  
Transcriptional Activation ◽  
Binding Free Energy ◽  
Energy Structure ◽  
Induced Fit ◽  
Hydrogen Bond Formation ◽  
Conformational Selection ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Region ◽  
Dissociation Mechanisms

<p>We investigate association and dissociation mechanisms of a typical intrinsically disordered region (IDR), transcriptional activation subdomain of tumor repressor protein p53 (TAD-p53) with murine double-minute clone 2 protein (MDM2). Using the combination of cycles of association and dissociation parallel cascade molecular dynamics, multiple standard MD, and Markov state model, we are successful in obtaining the lowest free energy structure of MDM2/TAD-p53 complex as the structure very close to that in crystal without prior knowledge. This method also reproduces the experimentally measured standard binding free energy, and association and dissociation rate constants solely with the accumulated MD simulation cost of 11.675 μs, in spite of the fact that actual dissociation occurs in the order of a second. Although there exist a few complex intermediates with similar free energies, TAD-p53 first binds MDM2 as the second lowest free energy intermediate dominantly (> 90% in flux), taking a form similar to one of the intermediate structures in its monomeric state. The mechanism of this step has a feature of conformational selection. In the second step, dehydration of the interface, formation of π-π stackings of the side-chains, and main-chain relaxation/hydrogen bond formation to complete α-helix take place, showing features of induced fit. In addition, dehydration (dewetting) is a key process for the final relaxation around the complex interface. These results demonstrate a more fine-grained view of the IDR association/dissociation beyond classical views of protein conformational change upon binding.</p>

From Selection to Instruction and Back — Competing Conformational Selection and Induced Fit Pathways in Abiotic Hosts

2021 ◽  
Author(s):  
Jovica D Badjic ◽  
Radoslav Z Pavlović ◽  
Remy F Lalisse ◽  
Alexandar L Hansen ◽  
Christopher A Waudby ◽  
...  
Keyword(s):  
Induced Fit ◽  
Conformational Selection

Conformational Selection versus Induced Fit in Kinases: The Case of PI3K-γ

2011 ◽  
Vol 51 (3) ◽  
pp. 642-646 ◽  
Author(s):  
Marco D'Abramo ◽  
Obdulia Rabal ◽  
Julen Oyarzabal ◽  
Francesco Luigi Gervasio
Keyword(s):  
Induced Fit ◽  
Conformational Selection

scholarly journals A Role for Both Conformational Selection and Induced Fit in Ligand Binding by the LAO Protein

2011 ◽  
Vol 7 (5) ◽  
pp. e1002054 ◽  
Author(s):  
Daniel-Adriano Silva ◽  
Gregory R. Bowman ◽  
Alejandro Sosa-Peinado ◽  
Xuhui Huang
Keyword(s):  
Ligand Binding ◽  
Induced Fit ◽  
Conformational Selection

scholarly journals Induced Fit Is a Special Case of Conformational Selection

Biochemistry ◽  
2017 ◽  
Vol 56 (22) ◽  
pp. 2853-2859 ◽  
Author(s):  
Pradipta Chakraborty ◽  
Enrico Di Cera
Keyword(s):  
Induced Fit ◽  
Conformational Selection ◽  
Special Case

scholarly journals Conformational propensities of intrinsically disordered proteins influence the mechanism of binding and folding

2015 ◽  
Vol 112 (31) ◽  
pp. 9614-9619 ◽  
Author(s):  
Munehito Arai ◽  
Kenji Sugase ◽  
H. Jane Dyson ◽  
Peter E. Wright
Keyword(s):  
Intrinsically Disordered Proteins ◽  
Terminal Region ◽  
Relaxation Dispersion ◽  
Disordered Proteins ◽  
Conformational Ensemble ◽  
Induced Fit ◽  
Conformational Selection ◽  
Intrinsically Disordered ◽  
Factor C ◽  
Binding Mechanisms

Intrinsically disordered proteins (IDPs) frequently function in protein interaction networks that regulate crucial cellular signaling pathways. Many IDPs undergo transitions from disordered conformational ensembles to folded structures upon binding to their cellular targets. Several possible binding mechanisms for coupled folding and binding have been identified: folding of the IDP after association with the target (“induced fit”), or binding of a prefolded state in the conformational ensemble of the IDP to the target protein (“conformational selection”), or some combination of these two extremes. The interaction of the intrinsically disordered phosphorylated kinase-inducible domain (pKID) of the cAMP-response element binding (CREB) protein with the KIX domain of a general transcriptional coactivator CREB-binding protein (CBP) provides an example of the induced-fit mechanism. Here we show by NMR relaxation dispersion experiments that a different intrinsically disordered ligand, the transactivation domain of the transcription factor c-Myb, interacts with KIX at the same site as pKID but via a different binding mechanism that involves elements of conformational selection and induced fit. In contrast to pKID, the c-Myb activation domain has a strong propensity for spontaneous helix formation in its N-terminal region, which binds to KIX in a predominantly folded conformation. The C-terminal region of c-Myb exhibits a much smaller helical propensity and likely folds via an induced-fit process after binding to KIX. We propose that the intrinsic secondary structure propensities of pKID and c-Myb determine their binding mechanisms, consistent with their functions as inducible and constitutive transcriptional activators.

scholarly journals Multiple conformational selection and induced fit events take place in allosteric propagation

2014 ◽  
Vol 186 ◽  
pp. 22-30 ◽  
Author(s):  
Ruth Nussinov ◽  
Buyong Ma ◽  
Chung-Jung Tsai
Keyword(s):  
Induced Fit ◽  
Conformational Selection
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