Please use this identifier to cite or link to this item: http://hdl.handle.net/20.500.12779/5338
Title: Construction and Validation of a RET TK Catalytic Domain by Homology Modeling
Authors: Tuccinardi, T
Manetti, Fabrizio 
Schenone, S
Martinelli, A
Botta, Maurizio 
Issue Date: 2007
Project: None 
Journal: JOURNAL OF CHEMICAL INFORMATION AND MODELING
Abstract: 
RET tyrosine kinase (TK) oncoproteins are potential targets for anticancer therapy. However, the search for novel RET inhibitors has been hampered by the lack of a 3D structure of the receptor. In this study, the "open" and the "closed" structure of the RET TK catalytic domain have been built by homology modeling techniques. The structures were validated by extensive docking studies with practically all the inhibitors reported in the literature and through molecular dynamics simulations of the resulting complexes. All the expected major interactions between the active domain amino acids and the inhibitors have been reproduced in their details. Furthermore, the proposed 3D models are in agreement with the results of available mutation studies. Therefore, these models could be profitably used to filter off from large libraries new potential hit compounds able to target this enzyme.
Description: 
38192
URI: http://hdl.handle.net/20.500.12779/5338
ISSN: 1549-9596
DOI: 10.1021/ci6004383
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