Molecular dynamics and energetic perceptions of substrate recognition by thymidylate kinase

Mahmoud Kandeel, Yoshihiro Noguchi, Kentaro Oh-Hashi, Hye Sook Kim, Yukio Kitade

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


Plasmodium deoxyguanylate pathways are an attractive area of investigation for future metabolic and drug discovery studies due to their unusual substrate specificities. We investigated the energetic contribution to thymidylate kinase substrate binding, and the forces underlying ligand recognition. The binding constant varied from 8 × 104 M-1 at 290 K to 6 × 104 M-1 at 310 K for dGMP, and from 16 × 104 M-1 at 290 K to 4 × 104 M -1 at 310 K for TMP. ΔC p was estimated as -1.75 kJ mol-1 K-1 for TMP and +2 kJ mol-1 K -1 for dGMP. In comparison with TMP, the binding of dGMP to PfTMK produced less favorable enthalpy change, positive or favorable entropic contribution at lower temperature, positive heat capacity change, negative \Updelta S-{\text{HE}}^{^\circ } Δ S HE â̂̃, positive ΔS other, higher total solvent-exposed surface area and more or less rigid body binding. These changes indicate unfavorable conditions for proper binding and lower conformational changes, and suboptimal structural reordering during dGMP binding.

Original languageEnglish
Pages (from-to)2089-2097
Number of pages9
JournalJournal of Thermal Analysis and Calorimetry
Issue number3
Publication statusPublished - Mar 2014


  • Isothermal titration calorimetry
  • Plasmodium falciparum
  • Thermodynamics
  • Thymidylate kinase

ASJC Scopus subject areas

  • Condensed Matter Physics
  • Physical and Theoretical Chemistry


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