TY - JOUR

T1 - Interfacing medicinal chemistry with structural bioinformatics

T2 - implications for T box riboswitch RNA drug discovery

AU - Jentzsch, Franziska

AU - Hines, Jennifer V

N1 - Funding Information: We wish to thank the National Institutes of Health (GM073188) for support of this work and the office of the VP for Research, Ohio University and the DAAD for support of FJ on an Internationale Studien-und Ausbildungspartnerschaften (ISAP) grant. This article has been published as part of BMC Bioinformatics Volume 13 Supplement 2, 2012: Proceedings from the Great Lakes Bioinformatics Conference 2011. The full contents of the supplement are available online at http://www.biomedcentral.com/bmcbioinformatics/supplements/13/S2 1Department of Chemistry, Leipzig University, Leipzig, Germany. 2Department of Chemistry & Biochemistry, Ohio University, Athens, OH, USA.

PY - 2012/3/13

Y1 - 2012/3/13

N2 - The 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. The ΔG of aminoacyl tRNA synthetase (aaRS) T box riboswitch terminators and antiterminators was predicted using DINAMelt and the resulting ΔΔG (ΔG Terminator - ΔG Antiterminator) values were compared. Average ΔΔG values did not differ significantly between the bacterial species analyzed, but there were significant differences based on the type of aaRS. The 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.

AB - The 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. The ΔG of aminoacyl tRNA synthetase (aaRS) T box riboswitch terminators and antiterminators was predicted using DINAMelt and the resulting ΔΔG (ΔG Terminator - ΔG Antiterminator) values were compared. Average ΔΔG values did not differ significantly between the bacterial species analyzed, but there were significant differences based on the type of aaRS. The 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.

KW - Chemistry

KW - Biology

UR - http://www.scopus.com/inward/record.url?scp=84875962933&partnerID=8YFLogxK

UR - https://www.mendeley.com/catalogue/4a71b2a5-4641-330e-8cf6-63eff3404650/

U2 - 10.1186/1471-2105-13-S2-S5

DO - 10.1186/1471-2105-13-S2-S5

M3 - Journal articles

C2 - 22536868

VL - 13 Suppl 2

SP - 1

EP - 5

JO - BMC Bioinformatics

JF - BMC Bioinformatics

SN - 1471-2105

IS - Suppl 2

M1 - S5

ER -