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. 2017 Jul 25;7:6398. doi: 10.1038/s41598-017-04905-0

Table 1.

Calculated and experimental relative binding free energies for 20 compound pairs based on adenine. 2D structures of the compounds are shown in Fig. 1C.

Ligand pair (A → B) cmpd A cmpd B ΔΔGbind (kcal/mol)
R1 R2 R1 R2 Experimentala Calculatedb
12 pocket A H CH3 <−1.6 −3.9 ± 0.2
3 → 4 Br CH3 Br H 2.0 ± 0.3 2.4 ± 0.0
5 → 3 Br CH3CH2 Br CH3 0.5 ± 0.3 −1.2 ± 0.0
6 → 5 Br HOCH2CH2 Br CH3CH2 −1.5 ± 0.2 −2.5 ± 0.1
7 → 5 Br CH3CH2CH2 Br CH3CH2 −1.1 ± 0.2 −0.5 ± 0.1
8 → 5 Br (CH3)2CHCH2 Br CH3CH2 −2.9 ± 0.3 −2.3 ± 0.1
9 → 2 H CH3CH2 H CH3 0.7 ± 0.2 0.2 ± 0.0
10 → 9 H HOCH2CH2 H CH3CH2 −1.0 ± 0.2 −1.4 ± 0.1
11→ 9 H (CH3)2CHCH2 H CH3CH2 <−2.3 −3.2 ± 0.0
12 → 13 H HOCH2CH2CH2 H CH3CH2CH2 0.5 ± 0.2 0.6 ± 0.4
3 →2 Pocket B Br CH3 H CH3 2.4 ± 0.2 2.3 ± 0.2
5 → 9 Br CH3CH2 H CH3CH2 2.2 ± 0.3 1.5 ± 0.0
14 → 15 Br cC5H9 H cC5H9 0.0 ± 0.3 −2.2 ± 0.2
16 → 17 Br CH2CHCH2CH2 H CH2CHCH2CH2 1.0 ± 0.2 0.3 ± 0.2
18 → 9 CH3 CH3CH2 H CH3CH2 1.4 ± 0.2 1.4 ± 0.0
19 → 9 furyl CH3CH2 H CH3CH2 3.8 ± 0.2 5.4 ± 0.2
20 → 9 OH CH3CH2 H CH3CH2 0.4 ± 0.2 0.1 ± 0.1
21 → 18 CH3O CH3CH2 CH3 CH3CH2 1.3 ± 0.1 2.7 ± 0.1
22 → 21 CH3CH2O CH3CH2 CH3O CH3CH2 −0.3 ± 0.2 −0.4 ± 0.0
23 → 21 (CH3)2CHO CH3CH2 CH3O CH3CH2 <−4.9/−0.8c 0.0 ± 0.1

aUncertainties are calculated as the standard error of the mean based on the maximal and minimal affinities values obtained from the 95% confidence intervals of the experimentally determined Ki values. Experimental Ki values can be found in Supplementary Table 1.

bAverage relative binding free energy from three independent trajectories with uncertainties estimated as the standard error of the mean.

cKi value from reference 23/Remeasured Ki value in this work (Supplementary Table 1).