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Showing 1 to 20 of 26 for “"induced fit"”.
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Induced-Fit Anion Sensing
… interest in their binding and sensing. In induced-fit anion sensing, the binding of an anion causes a shift in the equilibrium of conformers of the molecule, which in turn may lead to a change in a physical property. In this thesis four experimental chapters describe the synthesis and anion …
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Investigating the Role of Conformational Flexibility in tRNA Aminoacylation
… According to Koshland's classical "induced fit" model of enzyme regulation, proteins have essential conformational flexibility for ligand binding, which promotes catalysis by structural rearrangement. Proteins undergo structural rearrangements to bind ligands, regulate access to a …
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Modeling protein flexibility using collective modes of motion: Applications to drug design
… important macromolecular motions such as the induced fit process. Induced fit occurs during the binding of a protein to other proteins, nucleic acids or small molecules (ligands) and is a critical part of protein function. It is now widely accepted that conformational changes of proteins can …
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Elucidating binding modes of zuonin A enantiomers to JNK1 via in silico methods
… shows (-)-zuonin A interacting with JNK via an induced fit mechanism by forming a larger pocket for itself near the highly conserved [phi]A-X-[phi]B recognition site, a dynamic move not seen in (+)-zuonin A simulations, and may help explain their different inhibition patterns.
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Exploring Protein-Ligand Interaction with Rotamer-Library Based Refinement Tools
… This algorithm was used as part of an induced-fit binding protocol to refine and rank protein-ligand binding poses from apo and cross-docking test sets. The systematic optimization in this algorithm allows all-atom force fields to approach and in some cases exceed the accuracy of …
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Investigation of the dynamics and conformational changes of the U1A protein
… anisotropy data obtained here supports the induced fit mechanism of binding. Chapter 3 describes the kinetic studies of dissociation of the U1A-SL2 RNA complex using laser T-jump and stopped-flow fluorescence methods. Analysis of the kinetic data suggested three phases of dissociation with …
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On the origins of enzyme inhibitor selectivity and promiscuity: a case study of protein kinase binding to staurosporine
… the tetrahydropyran ring of staurosporine causes induced-fit of the glycine rich loop. I apply multiple linear regression to select distances measured between the distinctive parts of residues which correlate with the binding constants. This method allows me to understand the importance of the …
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Aufklärung des enzymatischen Mechanismus der L-Fuculose-1-phosphat-Aldolase aus Escherichia Coli durch ortsgerichtete Mutagenese und röntgenographische Untersuchungen
… Substratbindung das aktive Zentrum durch einen induced fit verschließt. In der Struktur des WT hatten diese Reste keine definierte Konformation. Durch die kinetischen Daten der C-terminalen Mutanten konnte jedoch nachgewiesen werden, daß die Reste Tyr209' und Glu214' höchstwahrscheinlich mit dem …
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Towards High-resolution Computational Approaches for Structure-based Drug Discovery
… discovery. IDSite is able to efficiently model induced-fit effects using flexible docking and constrained refinements. Sites of metabolism are determined based on the physical interactions between a P450 enzyme and the ligand. Preliminary tests with 56 compounds displayed both low false positive …
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Ligand and Protein Dynamics of CYP3A4
… small molecules. Chapter 2 details the ligand-induced effects on conformational dynamics of CYP3A4 via hydrogen-deuterium exchange mass spectrometry for the allosteric effector, midazolam (MDZ). The MDZ-induced effects on the structural dynamics of CYP3A4 are not confined to the active site and …
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On the Structural Adaptability and Dynamics of Metal-Organic Cages
… cavity size. The system exemplifies Koshland's induced-fit model, demonstrating synthetic assemblies can mimic biological macromolecule adaptability while maintaining structural integrity. The second approach extends this adaptability to the self-assembly of heteroleptic cages, using the same …
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Intrinsically disordered proteins in molecular recognition and structural proteomics
… the importance of intrinsic disorder and induced fit in molecular recognition. More generally, many intrinsically disordered regions that mediate interactions share similar features that are identifiable from protein sequence. Chapter IV reviews several models of IDP mediated …
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The molecular basis of nucleotide recognition for T7 DNA polymerase
… accounts for the high specificity following the induced fit mechanism. However, the identity of this rate-limiting conformational change and how it contributes to the fidelity is still under debate. An important study of T7 DNA polymerase performed by Tsai and Johnson using a conformationally …
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Opposing Actin Networks Modulate the Mechano-Activation of the Integrin LFA-1 During Immunological Synapse formation
… immobilized ligand, and is enhanced through the induced fit of ligand binding, alongside the enhanced tension provided by pulling on immobilized ICAM-1. Furthermore, I find that Dendritic Cells (DCs) are capable of modulating the lateral mobility of ICAM-1 on their plasma membrane during TLR …
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Designing Direct and Indirect Factor Xa Inhibitors
… by the pre–equilibrium pathway rather than the induced–fit mechanism utilized by heparin analogs. A similar interdisciplinary approach was exploited to design direct FXa inhibitors that possess high selectivity and are potentially orally bioavailable. Structurally, the designed direct FXa …
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Probing Order within Intrinsically Disordered Proteins
Decades have passed since the realisation that a protein’s amino acid sequence can contain all the information required to form a complex three-dimensional fold. Until recently, these encoded structures were thought to be crucial determinants of protein function. Much effort was directed to fully …
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Discovery of Novel Glycogen Synthase Kinase-3beta Inhibitors: Molecular Modeling, Virtual Screening, and Biological Evaluation
… and C-lobe hydrophobic groove, which will benefit the discovery of non-ATP-competitive inhibitors. To identify structurally novel and diverse compounds that effectively inhibit GSK-3â, we performed virtual screening by implementing a mixed ligand/structure-based approach, which included …
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Structural mechanism of the recovery-stroke in Myosin II molecular motor at atomic detail
… sie die Rolle hat die ATP Bindetasche durch "induced fit" zu formen.
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Stereoselectivity, kinetics, and engineering of flavin/deazaflavin oxidoreductases for use in industrial biocatalysis
… characterised by X-ray crystallography, and induced-fit docking (IFD) studies rationalised the opposite stereochemical outcome compared to the OYE family. A kinetic study and chiral GC/MS analysis revealed rather low turnover and moderate level of enantioselectivity in some cases. To improve …
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Stereoselectivity, kinetics, and engineering of flavin/deazaflavin oxidoreductases for use in industrial biocatalysis
… characterised by X-ray crystallography, and induced-fit docking (IFD) studies rationalised the opposite stereochemical outcome compared to the OYE family. A kinetic study and chiral GC/MS analysis revealed rather low turnover and moderate level of enantioselectivity in some cases. To improve …
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