当前位置： SCI文献检索 > JOURNAL OF BIOMOLECULAR STRUCTURE & DYNAMICS期刊下所有文献 > Molecular dynamics simulation of colchicinoids.

Molecular dynamics simulation of colchicinoids.

Abstract：

:Colchicine, a tricyclic alkaloid, has a remarkable range of biological activities. It binds with tubulin and prevents the formation of microtubules. This compound consists of a six membered aromatic ring (A ring), a seven membered troponoid ring (C ring) and another seven membered aliphatic ring (B ring). Using molecular mechanics and molecular dynamics simulations as tools, conformational analysis of colchicine and its several important analogs were done. Molecular mechanics studies show that conformational space of these molecules have one low energy region. Taking the low energy minima as the starting conformation, molecular dynamics simulation for 100 pico seconds is done for each of the analogs and molecular dynamics simulation in solution is done for three representative compounds colchicine,isocolchicine and A-C compound. Internal coordinate trajectories show that the value of the dihedral angle C9-C7-C1-C14 (phi), (C7-C1 bond connects the A and C ring), is within 40 degrees to 50 degrees for all the compounds with fluctuations less than 15 degrees. These calculations indicate that there is an overall similarity in the dynamically averaged structure of all the drugs. The A ring and B ring of the compounds are more or less rigid. The C ring is somewhat flexible, the average conformation and motional properties show overall similarity. The potential energy curve and dynamics behaviour of colchicine and isocolchicine suggests that the difference in binding property of colchine and isocolchicine may originate from the positional difference of carbonyl oxygen and methoxy group of C ring, which is the only difference in the structures of the two compounds and this has no effect on the motional property and average conformations of these two compounds. From our study it is proposed that the movements occuring at various positions of the drug molecules are significantly correlated. It is suggested that such correlated motion may play an important role in the biological property of these compounds.

journal_name

J Biomol Struct Dyn

journal_title

Journal of biomolecular structure & dynamics

authors

Bothra AK,Roy S,Bhattacharyya B,Mukhopadhyay C

doi

10.1080/07391102.1998.10508219

subject

Has Abstract

pub_date

1998-04-01 00:00:00

pages

999-1008

issue

eissn

0739-1102

issn

1538-0254

journal_volume

pub_type

杂志文章

在线工具

Molecular dynamics simulation of colchicinoids.