Nucleic acid - small molecule interactions, experimentally based molecular modeling approach

Grabar Branilović, Marina (2014) Nucleic acid - small molecule interactions, experimentally based molecular modeling approach. Doctoral thesis, Sveučilište u Zagrebu, Prirodoslovno-matematički fakultet.

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Abstract

Scope of this thesis is the computational, molecular modeling study of interactions between nucleic acids and organic compounds like bis-phenanthridinium derivatives, guanidiniocarbonyl-pyrrole-aryl conjugates, phosphonium dyes and translation (benzimidazole and diaminopiperidine) inhibitors of hepatitis C virus. They bind to polynucleotide in specific way, either as intercalators orgroovebindersandin addition establishstrong electrostatic interactions with polynucleotides. The first three groups of compounds have ability of molecular recognition of nucleobases so they can be used eitheras a template for development of thenew,highly specific nucleic acids markersor antiviral drugs with the ability to selectively block transcription of specific DNA/RNA sequences. Starting points for modeling were results of spectroscopic measurements(UV-Vis and CD spectra, fluorimetric titrations) and X-ray and NMR analysis. Study wasperformed using molecular modeling methods of various degrees of complexity.In order to determinate new parameters quantum mechanics calculations were used. The study of the structure and flexibility of nucleic acids and their complexes with small organic molecules was performed using the force field methods (molecular mechanics and molecular dynamics), while influence of the nucleic acid environment, precisely polynucleotide strand and metal ions, on the ligand charge distribution was investigated by the combined quantum mechanics –molecular mechanics approach. The results obtained within the research arein accordance with the experimental findings.

Item Type:	Thesis (Doctoral thesis)
Uncontrolled Keywords:	nucleic acids; force field; molecular mechanics; molecular dynamics quantum mechanical calculations; intercalators; minor groove binders; HCV inhibitors
Subjects:	NATURAL SCIENCES > Physics
Divisions:	Division of Physical Chemistry
Projects:	Project title Project leader Project code Project type Computational study of bio-macromolecules and development of new algorithms (Proučavanje biomakromolekula računalnim metodama i razvoj novih algoritama)- Sanja Tomić 098-1191344-2860 MZOS
Depositing User:	Marina Grabar Branilović
Date Deposited:	06 Oct 2015 14:46
URI:	http://fulir.irb.hr/id/eprint/2153

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