| Budget Amount *help |
¥41,210,000 (Direct Cost: ¥31,700,000、Indirect Cost: ¥9,510,000)
Fiscal Year 2015: ¥7,670,000 (Direct Cost: ¥5,900,000、Indirect Cost: ¥1,770,000)
Fiscal Year 2014: ¥8,970,000 (Direct Cost: ¥6,900,000、Indirect Cost: ¥2,070,000)
Fiscal Year 2013: ¥24,570,000 (Direct Cost: ¥18,900,000、Indirect Cost: ¥5,670,000)
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| Outline of Final Research Achievements |
We studied fragment-based drug discovery based on the biophysical methods, including isothermal titration calorimetry (ITC), surface plasmon resonance (SPR), and differential scanning calorimetry (DSC). The hit compounds bound specifically to target proteins; the interactions between compounds and the targets were validated using these biophysical measurements and the binding mechanisms have been characterized thermodynamically. We carried out X-ray crystallographic analyses and in silico docking simulation to discuss the thermodynamics of the interactions. The crystal structure and docking simulation supported thermodynamic data. Moreover, one hit compound was optimized to bind strongly to the target protein, of which dissociation constant showed sub-micro molar. This research provides a novel rational strategy to obtain the true-hit compounds through screening small molecule compounds.
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