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|Title: ||Molecular modelling and competition binding study of Br-noscapine and colchicine provide insight into noscapinoid-tubulin binding site|
|Authors: ||NAIK, PK|
|Keywords: ||VALENCE BASIS-SETS|
|Issue Date: ||2011|
|Publisher: ||ELSEVIER SCIENCE INC|
|Citation: ||JOURNAL OF MOLECULAR GRAPHICS & MODELLING,29(7)947-955|
|Abstract: ||We have previously discovered the tubulin-binding anti-cancer properties of noscapine and its derivatives (noscapinoids). Here, we present three lines of evidence that noscapinoids bind at or near the well studied colchicine binding site of tubulin: (1) in silico molecular docking studies of Br-noscapine and noscapine yield highest docking score with the well characterised colchicine-binding site from the co-crystal structure; (2) the molecular mechanics-generalized Born/surface area (MM-GB/SA) scoring results Delta Delta G(bind-cald) for both noscapine and Br-noscapine (3.915 and 3.025 kcal/mol) are in reasonably good agreement with our experimentally determined binding affinity (Delta Delta G(bind-Expt) of 3.570 and 2.988 kcal/mol, derived from K(d) values); and (3) Br-noscapine competes with colchicine binding to tubulin. The simplest interpretation of these collective data is that Br-noscapine binds tubulin at a site overlapping with, or very close to colchicine-binding site of tubulin. Although we cannot rule out a formal possibility that Br-noscapine might bind to a site distinct arid distant from the colchicine-binding site that might negatively influence the colchicine binding to tubulin. (C) 2011 Elsevier Inc. All rights reserved.|
|Appears in Collections:||Article|
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