Hochschulschrift
Modeling protein dynamics in solution: effects of ligand binding and crowding
Zusammenfassung: In this thesis, molecular dynamics simulations have been performed to understand the effect of ligand binding or crowding on the structure and dynamics of proteins or peptides.Our findings show a long-range conformational response of the PDZ2 domain of human tyrosine phosphatase 1E to ligand release in the form of a collective shift of several rigid secondary structure elements and the C terminal loop relative to the rest of the protein away from the N-terminus.Considering a multi-domain protein as a next step, the allosteric coupling in the ligand-controlled oligomeric bacterial protease DegS between the active site and (i) the binding pocket of the ligand, as well as (ii) the sites in contact with other protomers has been analyzed. Our results indicate that only trimeric and not monomeric DegS is functional. The pathways via which ligand release or the disassembly of DegS into monomers leads to response at functionally relevant allosteric sites are revealed.Finally, we have the relationship between biomolecular conformational changes and water mediation in crowded environments. We find that molecular crowding, though barely changing the structural distribution of the peptide, substantially affects the kinetics of conformational changes. In view of the weak interaction between the peptides observed (a prerequisite for good crowders), our results provide evidence for a non-trivial role of the solvent for the slowing down in the kinetics of conformational transitions of the peptides
- Location
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Deutsche Nationalbibliothek Frankfurt am Main
- Extent
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Online-Ressource
- Language
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Englisch
- Notes
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Albert-Ludwigs-Universität Freiburg, Dissertation, 2015
- Classification
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Biowissenschaften, Biologie
- Keyword
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Molekulardynamik
Allosterie
- Event
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Veröffentlichung
- (where)
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Freiburg
- (who)
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Universität
- (when)
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2016
- Creator
- Contributor
- DOI
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10.6094/UNIFR/10493
- URN
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urn:nbn:de:bsz:25-freidok-104936
- Rights
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Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Last update
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14.08.2025, 10:46 AM CEST
Data provider
Deutsche Nationalbibliothek. If you have any questions about the object, please contact the data provider.
Object type
- Hochschulschrift
Associated
- Lu, Cheng
- Stock, Gerhard
- Universität
Time of origin
- 2016
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Template-based modeling of insect odorant receptors outperforms AlphaFold3 for ligand binding predictions
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Modeling the effects of molecular crowding on cerebellar long term depression
Ligand 1 H NMR Chemical Shifts as Accurate Reporters for Protein‐Ligand Binding Interfaces in Solution **
Solution NMR structure of a ligand/hybrid-2-G-quadruplex complex reveals rearrangements that affect ligand binding
Predicting target-ligand interactions using protein ligand-binding site and ligand substructures
Derangement model of ligand-receptor binding
Conformational Changes in Ligand Binding Processes
Crowding In or Crowding Out? A Classical-Harrodian Perspective
How odgcrnwi becomes crowding: Stimulus-specific learning reduces crowding
Role of Macromolecular Crowding on the Intracellular Diffusion of DNA Binding Proteins
Template-based modeling of insect odorant receptors outperforms AlphaFold3 for ligand binding predictions
Foveal Crowding Resolved
Prediction of protonation states in ligand-protein complexes upon ligand binding
Modeling the effects of molecular crowding on cerebellar long term depression
Ligand 1 H NMR Chemical Shifts as Accurate Reporters for Protein‐Ligand Binding Interfaces in Solution **
Solution NMR structure of a ligand/hybrid-2-G-quadruplex complex reveals rearrangements that affect ligand binding
Predicting target-ligand interactions using protein ligand-binding site and ligand substructures
Derangement model of ligand-receptor binding
Conformational Changes in Ligand Binding Processes
Crowding In or Crowding Out? A Classical-Harrodian Perspective
How odgcrnwi becomes crowding: Stimulus-specific learning reduces crowding
Role of Macromolecular Crowding on the Intracellular Diffusion of DNA Binding Proteins
Template-based modeling of insect odorant receptors outperforms AlphaFold3 for ligand binding predictions
Foveal Crowding Resolved
Prediction of protonation states in ligand-protein complexes upon ligand binding