Structure-Activity Relationships of a Caged Thrombin-Binding DNA Aptamer: Insight gained from molecular dynamics simulation studies

P. Jayapal, G. Mayer, A. Heckel, F. Wennmohs

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)


15-mer ssDNA aptamers play a vital role in the inhibition of alpha-thrombin in the blood clotting mechanism. It is of high importance to explore the structural factors controlling the inhibitory nature of the aptamer. Here we investigated the structure-function relationship of the anti-thrombin aptamer, as well as its 'caged' variant (2-(2-nitrophenyl)-propyl group (NPP)) by molecular dynamics simulations. The stability of the unmodified aptamer at different temperatures is examined in 2ns all-atom simulations and compared to experiment. The change in structure when introducing the photo-labile caged compound is analyzed, and the regiospecificity of this modification explained on atomic level. Removal of the photo-labile group leads to the reformation of the active aptamer structure from its inactive state. The mechanism for this formation process is a concerted movement of the aptamer backbone and some highly important bases. The binding of the aptamer to thrombin with regard to the 'caged' group is studied in an explicit simulation with the aptamer-thrombin complex and the reason for the binding/unbinding nature of the aptamer shown.
Original languageEnglish
Pages (from-to)241-250
Number of pages9
JournalJournal of Structural Biology
Issue number3
Publication statusPublished - 2009


  • nucleotide aptamers
  • computer simulation
  • hydrogen bonding
  • molecular models
  • caging
  • classical molecular dynamic simulation
  • hoogsteen hydrogen bonding
  • photo-labile group
  • alpha-thrombin
  • thrombin binding aptamer
  • quadruplex
  • c-myc promoter
  • g-quadruplex
  • thermodynamic analysis
  • induced stabilization
  • stability
  • oligonucleotides
  • transition
  • inhibitor
  • duplex
  • motif
  • molecular structure
  • protein binding
  • structure-activity relationship
  • temperature
  • thermodynamics


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