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Moretti, Loris (2007) Exploring Structure and Plasticity of Tyrosine Kinase Domains for Drug Discovery. [Tesi di dottorato]

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Abstract (inglese)

Protein tyrosine kinases (TKs) play a crucial role in human physiology and their abnormal function, due to protein modifications, is correlated with several diseases.

The clear need to understand the mechanisms and to antagonize the activities of aberrant catalytic domains of TKs (KD) fired up this thesis. Through the chapters, evaluations about sequence, structure, dynamics and ligand binding of these proteins are made using several computational tools.

Firstly, the essential structural elements for molecules to bind at the ATP-binding site are defined. Then, the dynamical behavior of different KDs is classified based on the rearrangement of 5 clusters of residues. In particular, a pool of residues, found at the interface of the two lobes, appears to be important for the protein conformation and motion.
Finally, the investigation about the activation mechanism of oncogenic Flt3 is reported and a secondary structure element suggested as the first driving force for conformational changes.


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Tipo di EPrint:Tesi di dottorato
Relatore:Scapozza, Leonardo - Moro, Stefano
Dottorato (corsi e scuole):Ciclo 20 > Scuole per il 20simo ciclo > SCIENZE MOLECOLARI > SCIENZE FARMACEUTICHE
Data di deposito della tesi:2007
Anno di Pubblicazione:2007
Informazioni aggiuntive:un CD-ROM in annesso con dati riguardanti la tesi
Parole chiave (italiano / inglese):Molecular Modelling, Tyrosine kinase plasticity, tyrosine kinase domain
Settori scientifico-disciplinari MIUR:Area 03 - Scienze chimiche > CHIM/08 Chimica farmaceutica
Struttura di riferimento:Dipartimenti > Dipartimento di Scienze Farmaceutiche
Codice ID:346
Depositato il:10 Set 2008
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