Naslov
Bisphenanthridinium-nucleobase conjugates – molecular modelling and spectroscopic approach

Autori
Grabar, Marina ; Tumir, Lidija-Marija ; Piantanida, Ivo ; Tomić, Sanja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, ostalo

Izvornik
Book of Abstracts of the EMBO Young Scientists Forum / - Zagreb, 2009

Skup
EMBO Young Scientists Forum

Mjesto i datum
Zagreb, Hrvatska, 15.06.2009. - 17.06.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Nije recenziran

Ključne riječi
nucleobase conjugates of bisphenantridinium; molecular modelling; program Amber; stacked conformation; spectroscopy

Sažetak
The subject of this work is study on nucleobase conjugates of bisphenantridinium and their complexes with nucleotides. It shows how molecular modelling, particularly the long time molecular dynamics simulations (MD) can be used to rationalize the experimental results on molecules and their complexes. Accordingly, molecular modelling results in combination with the spectroscopic measurements for a series of nucleobase conjugates of bisphenanthridinium as well as their non-covalent complexes with UMP and AMP are presented. AMBER ff03 and GAFF force fields were used to parametrize molecules and Molecular Dynamics (MD) simulations of solvated molecules and their complexes were accomplished with the program AMBER9. During the MD simulations initial folded conformations of some molecules relaxed ; however majority of molecules remained in their folded, more or less stacked conformation with no water molecules accommodated within the two phenanthridinium rings. The adenine derivative of bisphenantridin nucleobase conjugates revealed highly selective affinity toward complementary nucleotide. The initial structure of its complex with UMP was built in a way to enable adenine and uracil from UMP to form the Watson-Crick type of H-bonds. During the MD simulation the conformation of the complex changed and stabilized in a conformation with adenine in the stacking interaction with one phenanthridinium ring, and uracil with the other. In this interaction the hydrophobic pocket made by two phenanthridinium rings and the alkyl linker is very functional since there is no water molecule within it to compete with uracil from UMP for the hydrogen bond. The obtained results performed for its complexes with AMP and UMP are in agreement with the experimentally determined spectroscopic results and the measured binding affinities.

Izvorni jezik
Engleski

Znanstvena područja
Fizika, Kemija

POVEZANOST RADA