Interfacing medicinal chemistry with structural bioinformatics: implications for T box riboswitch RNA drug discovery

BMC Bioinformatics

Proceedings

Jennifer V Hines¹  Franziska Jentzsch² 

[1] Department of Chemistry & Biochemistry, Ohio University, Athens, OH, USA;Department of Chemistry, Leipzig University, Leipzig, Germany;Department of Chemistry & Biochemistry, Ohio University, Athens, OH, USA;

关键词: Free Energy;    Quantitative Structure Activity Relationship;    Aminoacyl tRNA Synthetase;    Clostridium Botulinum;    Glycyl;   

DOI  :  10.1186/1471-2105-13-S2-S5

来源: Springer

【 摘 要 】

BackgroundThe T box riboswitch controls bacterial transcription by structurally responding to tRNA aminoacylation charging ratios. Knowledge of the thermodynamic stability difference between two competing structural elements within the riboswitch, the terminator and the antiterminator, is critical for effective T box-targeted drug discovery.MethodsThe ΔG of aminoacyl tRNA synthetase (aaRS) T box riboswitch terminators and antiterminators was predicted using DINAMelt and the resulting ΔΔG (ΔGTerminator - ΔGAntiterminator) values were compared.ResultsAverage ΔΔG values did not differ significantly between the bacterial species analyzed, but there were significant differences based on the type of aaRS.ConclusionsThe data indicate that, of the bacteria studied, there is little potential for drug targeting based on overall bacteria-specific thermodynamic differences of the T box antiterminator vs. terminator stability, but that aaRS-specific thermodynamic differences could possibly be exploited for designing drug specificity.

【 授权许可】

CC BY   
© Jentzsch and Hines; licensee BioMed Central Ltd. 2012