Table 3.

Average values of binding free energy and enthalpy for fragment-derived compounds binding to Astex protein targets. 5-fold affinity ranges have been selected that cover distinct stages of the drug design process. Our error analysis for ITC measurements is discussed in supplemental information (available online) and indicates that ΔG and ΔH are measured with standard deviations of ± 0.1 kcal/mol and ±0.4 kcal/mol respectively. For replicate titrations which use solutions taken from the same stocks, the variation in ΔH can be reduced to ±0.2 kcal/mol or better.

Affinity Range (μM)	Description	Number of measurements	<ΔG> kcal/mol	<ΔH> kcal/mol
50–250	Fragment Screening Hits	21	−5.4	−5.5
1–5	Optimized Fragment Hits	40	−7.8	−6.9
0.02 – 0.10	Fragment-derived Leads	40	−10	−12
0.002 – 0.0004	Optimized Leads	48	−11.8	−10.6