Electronic Supplementary Materia

Incorporating Specificity into Optimization: Evaluation of SPA Using CSAR 2014 and CASF 2013 Benchmarks

Zhiqiang Yan1, Jin Wang1,2,*

1 State Key Laboratory of Electroanalytical Chemistry, Changchun Institute of AppliedChemistry, Chinese Academy of Sciences, Changchun, Jilin 130022, China

2 Department of Chemistry & Physics, State University of New York at Stony Brook,Stony Brook, NY 11794-3400, USA

∗ E-mail:

Figure S1. Typical atom-pair interaction potentials of SPA 2.0. (A and B) Two of the most frequently occurred atom pairs related to hydrophobic interactions. (C and D) Atom pairs related to hydrogen bonds. (E and F) Atom pairs involving phosphorus and fluorine atoms.

Table S1. 22 Atom types used for calculating interactions based on the SYBYL definition. The atom types can be converted from PDB files by software BABEL

Type / Description / Type / Description
C.3 / carbon sp3 / N.4 / quaternary nitrogen
C.2 / carbon sp2 / O.3 / oxygen sp3
C.1 / carbon sp / O.2 / oxygen sp2
C.ar / carbon aromatic / O.co2 / carboxyl oxygen
C.cat / other carbons / S.3 / sulfur sp3
N.3 / nitrogen sp3 / S.2 / sulfur sp2
N.2 / nitrogen sp2 / S.O2 / sulfone sulfur
N.1 / nitrogen sp / P.3 / phosphorous sp3
N.ar / nitrogen aromatic / F / fluorine
N.p13 / trigonal nitrogen / Cl / chlorine
N.am / nitrogen amide / I/Bra / iodine/bromine

aThe atom types I and Br are grouped as one due to their low occurrences.

Table S2.101 effective types of atom pairs and their potentials of SPA2.0 for the protein-ligand interactions

Number / Atom Pair / Bin 1 / Bin 2 / Bin 3 / Bin 4 / Bin 5 / Bin 6 / Bin 7 / Bin 8 / Bin 9 / Bin 10 / Bin 11 / Bin 12 / Bin 13 / Bin 14 / Bin 15 / Bin 16
1 / C.3:C.3 / 15.45 / 9.27 / 8.05 / 4.96 / 0.29 / 0.10 / 0.04 / 0.01 / -0.15 / -0.46 / -0.37 / -0.22 / -0.27 / -0.24 / -0.04 / -0.09
2 / C.3:C.2 / 5.15 / 4.98 / 4.64 / 3.99 / 0.30 / 0.10 / 0.02 / -0.58 / -0.74 / -0.32 / -0.01 / -0.13 / -0.03 / -0.13 / -0.04 / -0.12
3 / C.3:C.1 / 5.15 / 3.18 / 3.24 / 3.55 / 0.07 / -1.57 / -1.05 / -0.92 / -1.65 / -0.03 / -1.07 / 0.00 / -0.69 / -0.11 / -0.19 / -0.16
4 / C.3:C.a / 5.15 / 5.20 / 6.69 / 4.65 / 0.13 / 0.00 / -0.51 / -0.60 / -0.38 / -0.52 / -0.26 / -0.19 / -0.03 / -0.02 / -0.01 / -0.00
5 / C.3 :C.cat / 5.15 / 3.18 / 4.76 / 2.62 / 0.24 / 0.14 / 0.06 / -0.57 / -0.08 / -0.03 / -0.59 / -0.05 / -0.02 / -0.04 / -0.22 / -0.17
6 / C.3:N.3 / 5.44 / 5.03 / 4.20 / 2.07 / 0.25 / 0.09 / 0.07 / 0.01 / -0.00 / -0.76 / -0.13 / -0.04 / -0.03 / -0.03 / -0.05 / -0.19
7 / C.3:N.2 / 27.23 / 7.66 / 10.19 / 0.29 / 0.11 / 0.04 / 0.03 / 0.01 / -0.43 / -0.94 / -1.18 / -1.25 / -0.73 / -0.10 / -0.05 / -0.03
8 / C.3:N.1 / 5.44 / 7.20 / 5.20 / 0.11 / -1.82 / -1.55 / -1.74 / -1.89 / -0.52 / -0.32 / -0.01 / -0.24 / 0.09 / -0.09 / -0.27 / -0.41
9 / C.3:N.ar / 5.44 / 7.44 / 4.75 / 0.32 / 0.04 / -0.89 / -0.01 / -0.09 / -0.03 / -0.04 / -0.12 / -0.02 / -0.02 / -0.01 / -0.01 / -0.01
10 / C.3:N.am / 5.44 / 3.68 / 2.52 / 0.55 / 0.28 / 0.15 / 0.09 / 0.13 / 0.16 / -0.11 / -0.03 / -0.04 / -0.04 / -0.05 / -0.06 / -0.07
11 / C.3 :N.pl3 / 5.44 / 4.03 / 5.08 / 2.00 / 0.09 / -0.15 / -0.31 / -0.00 / -0.03 / -0.05 / -0.03 / -0.03 / -0.03 / -0.00 / -0.01 / -0.02
12 / C.3:O.3 / 6.77 / 7.40 / 4.05 / 0.12 / 0.00 / 0.00 / 0.37 / 0.67 / -0.14 / -0.01 / -0.02 / -0.03 / -0.03 / -0.03 / -0.03 / -0.03
13 / C.3:O.2 / 6.77 / 8.12 / 3.10 / 0.06 / -0.56 / -0.44 / 0.01 / 0.33 / 0.12 / 0.02 / 0.01 / -0.21 / -0.34 / -0.31 / -0.28 / -0.38
14 / C.3 :O.co2 / 6.77 / 5.88 / 3.90 / -0.61 / -1.73 / -0.88 / -0.02 / -0.00 / -0.01 / -0.01 / -0.01 / -0.01 / -0.01 / -0.00 / 0.10 / 0.03
15 / C.3:S.3 / 11.87 / 8.65 / 12.81 / 6.50 / 0.11 / -1.07 / -0.89 / -0.97 / -1.31 / -0.71 / -1.03 / -0.54 / -0.01 / -0.34 / -0.24 / -0.32
16 / C.3:S.2 / 47.51 / 22.49 / 12.41 / 4.56 / 0.07 / -0.88 / -0.06 / -0.55 / -0.88 / -0.85 / -0.63 / -0.03 / -0.58 / -0.92 / -0.22 / 0.00
17 / C.3:S.O2 / 142.53 / 4.99 / 1.61 / 2.91 / 4.54 / 1.18 / 0.04 / -1.25 / -3.24 / -2.08 / -0.85 / -0.03 / 0.17 / -1.45 / 0.00 / -0.03
18 / C.3:P.3 / 14.59 / 6.26 / 2.22 / 2.02 / 0.43 / 0.09 / -0.59 / -1.20 / -0.95 / -0.95 / 0.04 / 0.63 / -0.00 / -0.01 / -0.04 / -0.05
19 / C.3:F / 10.07 / 11.20 / 2.66 / 0.03 / -1.13 / -0.89 / -0.06 / -0.17 / -0.61 / -0.06 / -0.77 / -0.01 / -0.01 / -0.43 / -0.00 / 0.00
20 / C.3:Cl / 20.64 / 8.14 / 11.24 / 4.79 / -1.95 / -2.55 / -0.13 / -1.16 / -1.97 / -0.06 / -0.75 / -0.24 / 0.02 / 0.01 / 0.00 / 0.00
21 / C.3:I / 43.82 / 15.64 / 13.24 / 8.47 / 0.44 / -2.00 / -0.12 / -0.06 / -1.49 / -1.50 / -0.97 / -0.15 / -0.37 / 0.49 / 0.79 / 0.72
22 / C.2:C.2 / 5.15 / 2.12 / 3.97 / 2.92 / 0.43 / 0.13 / 0.08 / -0.11 / -1.32 / -0.06 / -0.03 / -0.04 / -0.04 / -0.03 / -0.02 / -0.11
23 / C.2:C.ar / 5.15 / 2.12 / 3.47 / 1.69 / 0.23 / 0.08 / 0.03 / 0.00 / -0.25 / -0.01 / -0.02 / -0.03 / -0.03 / -0.05 / -0.05 / -0.05
24 / C.2 :C.cat / 61.80 / 5.30 / 5.40 / 0.69 / 0.39 / -0.46 / -0.17 / -0.36 / -0.07 / -0.83 / 0.08 / 0.20 / 0.04 / 0.01 / -0.09 / 0.00
25 / C.2:N.3 / 5.44 / 6.37 / 6.52 / 1.30 / -1.48 / -0.88 / 0.57 / 1.93 / -0.04 / -0.03 / -0.01 / -0.09 / -0.01 / -0.13 / -0.02 / -0.03
26 / C.2:N.2 / 10.89 / 9.85 / 5.20 / 0.23 / 0.01 / 0.19 / 0.00 / 0.03 / 0.21 / -0.33 / 0.37 / -0.00 / 0.20 / -0.84 / -0.68 / -0.81
27 / C.2:N.ar / 10.89 / 9.85 / 5.87 / 0.28 / 0.07 / 0.00 / 0.01 / 0.01 / 0.00 / -0.00 / -0.02 / -0.03 / -0.03 / -0.03 / -0.03 / -0.05
28 / C.2:N.am / 5.44 / 4.83 / 1.72 / 1.24 / 0.16 / -0.28 / 0.06 / 0.09 / 0.13 / -0.00 / -0.19 / -0.07 / -0.05 / -0.04 / -0.02 / -0.04
29 / C.2 :N.pl3 / 10.89 / 8.20 / 7.27 / 1.86 / -0.97 / -0.68 / -0.01 / -0.08 / -0.01 / -0.02 / -0.02 / -0.03 / -0.01 / -0.00 / 0.21 / 0.00
30 / C.2:O.3 / 6.77 / 7.81 / 3.05 / 0.00 / -1.35 / -0.57 / 0.13 / 0.24 / 0.01 / 0.02 / -0.01 / -0.02 / -0.02 / -0.03 / -0.02 / -0.03
31 / C.2:O.2 / 6.77 / 5.38 / 0.94 / 0.20 / -0.06 / -0.03 / -0.39 / 0.25 / -0.00 / 0.01 / 0.26 / -0.00 / -0.39 / -0.03 / -0.03 / -0.05
32 / C.2 :O.co2 / 3.38 / 5.66 / 3.65 / 0.15 / -1.04 / -0.51 / 0.02 / 0.02 / -0.01 / -0.02 / -0.03 / -0.03 / -0.02 / -0.01 / -0.01 / -0.01
33 / C.2:S.3 / 11.87 / 4.99 / 4.47 / 0.34 / 0.14 / 0.04 / -0.14 / -0.01 / -2.34 / -0.56 / 0.11 / -0.04 / -0.03 / -0.93 / -0.42 / -0.00
34 / C.2:S.2 / 59.39 / 22.49 / 13.49 / 0.43 / 0.09 / 0.14 / -0.18 / 0.06 / -0.40 / -0.21 / 0.01 / 0.03 / -0.43 / -1.06 / -0.05 / -0.07
35 / C.2:S.O2 / 130.65 / 44.99 / 13.49 / 2.26 / 0.92 / 5.09 / 4.02 / 0.13 / -2.18 / 0.04 / -3.36 / -0.66 / -0.79 / -1.72 / -0.85 / -0.06
36 / C.2:P.3 / 29.19 / 6.26 / 2.12 / 0.14 / 2.02 / 2.50 / 0.02 / -1.52 / -1.54 / -0.26 / -0.01 / -0.05 / -0.04 / -0.03 / -0.02 / -0.01
37 / C.2:F / 2.51 / 3.34 / 0.38 / 0.14 / 0.55 / 0.00 / 0.01 / 0.68 / 1.03 / -0.48 / 0.00 / -0.02 / -0.18 / -0.03 / -0.75 / -0.27
38 / C.ar:C.ar / 5.15 / 5.77 / 4.87 / 1.04 / 0.02 / -1.07 / -0.19 / -0.62 / -0.41 / -0.21 / -0.25 / -0.02 / -0.02 / -0.06 / -0.00 / -0.17
39 / C.ar: C.cat / 5.15 / 4.24 / 1.95 / 2.93 / 0.01 / -0.80 / -0.02 / -0.03 / -0.51 / -0.03 / -0.02 / -0.02 / -0.03 / -0.01 / -0.01 / -0.01
40 / C.ar:N.3 / 5.44 / 5.81 / 1.88 / 1.29 / 0.06 / -0.15 / 0.18 / -0.86 / -0.87 / -0.60 / -0.53 / -0.86 / -0.02 / -0.01 / 0.00 / 0.36
41 / C.ar:N.2 / 59.91 / 8.75 / 6.99 / 0.23 / -0.37 / -0.00 / -0.88 / -1.16 / -0.00 / -1.44 / -0.02 / -0.28 / -0.01 / -0.09 / 0.30 / -0.00
42 / C.ar:N.ar / 5.44 / 4.72 / 2.90 / 0.23 / -0.16 / -0.78 / -0.05 / -0.18 / -0.05 / -0.11 / -0.02 / -0.02 / -0.01 / -0.01 / 0.04 / -0.10
43 / C.ar:N.am / 5.44 / 4.75 / 1.79 / 0.99 / 0.19 / 0.08 / 0.06 / 0.04 / 0.01 / -0.34 / -0.14 / -0.12 / -0.09 / -0.05 / -0.05 / -0.06
44 / C.ar:N.pl3 / 5.44 / 2.73 / 4.54 / 0.24 / 0.00 / -1.07 / -0.57 / -0.02 / -0.04 / -0.02 / -0.03 / -0.02 / -0.01 / -0.01 / -0.01 / -0.00
45 / C.ar:N.4 / 21.78 / 13.13 / 3.12 / 0.34 / 0.38 / 0.27 / -0.20 / -1.49 / -0.97 / -0.77 / -0.04 / -0.02 / 0.87 / 0.14 / 2.33 / 0.07
46 / C.ar:O.3 / 6.77 / 8.20 / 1.26 / 0.12 / 0.01 / -0.00 / 0.13 / -0.01 / -0.35 / -0.05 / -0.03 / -0.03 / -0.03 / -0.01 / -0.00 / 0.07
47 / C.ar:O.2 / 6.77 / 7.31 / 2.83 / 0.14 / 0.03 / 0.01 / 0.01 / 0.00 / 0.00 / 0.00 / -0.10 / -0.50 / -0.15 / -0.12 / -0.03 / -0.04
48 / C.ar:O.co2 / 3.38 / 6.89 / 3.02 / 0.13 / 0.01 / 0.03 / 0.04 / 0.02 / -0.00 / -0.22 / -0.02 / -0.37 / -0.03 / -0.02 / -0.03 / -0.04
49 / C.ar:S.3 / 11.87 / 7.49 / 6.61 / 2.97 / 0.09 / -0.76 / -0.78 / -0.73 / -1.34 / -0.63 / -0.04 / -0.87 / -0.43 / -0.00 / 0.01 / 0.03
50 / C.ar:S.2 / 95.02 / 2.49 / 6.47 / 7.95 / 1.12 / -1.48 / -0.63 / 0.59 / 0.48 / 0.04 / 0.00 / -0.01 / -0.46 / -0.24 / -1.57 / -0.08
51 / C.ar:S.O2 / 225.68 / 2.49 / 3.77 / 2.26 / 2.83 / -0.61 / 1.55 / -0.12 / -2.63 / 0.00 / -1.02 / -0.35 / -0.71 / 0.11 / 0.07 / -0.88
52 / C.ar:P.3 / 58.39 / 3.13 / 2.83 / 2.68 / 1.42 / 0.31 / 0.05 / -1.57 / -1.64 / -0.04 / -0.00 / -0.05 / -0.68 / -0.05 / -0.09 / -0.03
53 / C.ar:F / 10.07 / 7.50 / 6.32 / 0.05 / -1.22 / -0.14 / -0.03 / -0.02 / -0.49 / -0.02 / -0.68 / -0.04 / 0.01 / -0.00 / 0.27 / -0.00
54 / C.cat:N.am / 5.44 / 1.09 / 0.20 / 0.57 / 7.35 / 3.58 / 1.96 / 0.08 / 1.59 / 0.70 / -0.07 / -0.18 / -0.10 / -0.05 / -0.06 / -0.04
55 / C.cat:O.3 / 16.94 / 10.04 / 3.07 / 0.56 / -1.84 / -1.59 / -0.05 / 0.09 / 0.43 / -0.01 / -0.01 / -0.05 / -0.01 / -0.00 / 0.03 / 0.03
56 / C.cat:O.2 / 3.38 / 7.00 / 4.01 / -0.59 / -3.25 / -3.15 / -0.37 / 0.01 / 0.15 / 0.16 / -0.01 / -0.31 / -0.00 / -0.02 / 0.11 / 0.38
57 / C.cat:O.co2 / 6.77 / 0.73 / 5.57 / -0.10 / -0.75 / -0.26 / -0.05 / 0.82 / 0.68 / 0.69 / 0.02 / 0.03 / 0.09 / 0.79 / 0.12 / 0.22
58 / N.3:N.ar / 5.70 / 1.09 / 0.00 / -2.31 / -2.31 / 0.14 / 0.05 / 1.80 / 0.03 / -0.70 / -0.48 / 0.04 / 0.03 / 0.73 / 0.03 / 1.15
59 / N.3:N.am / 5.70 / 2.01 / 0.49 / 3.29 / 0.65 / 0.44 / 1.65 / -0.38 / -1.24 / -0.03 / 0.04 / -0.02 / -0.03 / -0.49 / -0.07 / -0.05
60 / N.3:N.pl3 / 5.70 / 0.65 / 1.67 / 1.59 / 0.18 / 1.59 / 0.06 / 0.07 / -0.03 / -0.02 / -1.98 / -0.03 / -2.09 / -0.13 / 0.00 / -0.00
61 / N.3:O.3 / 3.47 / -4.84 / -3.14 / -0.44 / 0.82 / 0.02 / -0.39 / -0.03 / -0.02 / -0.05 / 0.00 / 0.01 / 1.10 / 0.95 / 0.09 / 0.98
62 / N.3:O.2 / 3.47 / -2.07 / -1.91 / 0.04 / 0.12 / 1.76 / 0.57 / 1.13 / 0.05 / 1.03 / 0.00 / 0.37 / 0.30 / -0.09 / -0.03 / -0.06
63 / N.3:O.co2 / 3.47 / -0.84 / -0.21 / -0.14 / -0.08 / -0.05 / -1.26 / -0.00 / -0.80 / -1.00 / -0.92 / -0.02 / 2.16 / 1.89 / 0.13 / 0.12
64 / N.ar:N.ar / 11.41 / 0.56 / 0.46 / 0.08 / -0.02 / 0.10 / 0.01 / -0.60 / -0.00 / -0.01 / -0.01 / -0.77 / -0.04 / -0.05 / -0.02 / 0.59
65 / N.ar:N.am / 5.70 / 0.57 / 0.11 / 0.15 / 0.15 / 0.12 / 0.07 / 0.04 / -0.07 / -0.00 / -0.28 / -0.01 / -0.20 / -0.04 / -0.05 / -0.18
66 / N.ar: N.pl3 / 11.41 / 3.22 / 0.72 / 0.05 / -0.97 / -0.96 / -1.20 / -0.01 / -0.37 / -0.03 / 0.48 / -0.00 / -0.01 / 0.20 / -0.01 / -0.01
67 / N.ar:O.3 / 3.47 / -2.03 / -0.09 / -0.02 / -0.00 / 0.02 / 0.02 / 0.00 / -0.61 / -0.06 / -0.01 / -0.00 / 0.06 / 0.28 / 0.09 / 0.76
68 / N.ar:O.2 / 3.47 / 0.22 / 0.13 / 0.12 / 0.00 / 0.02 / 0.03 / 0.03 / 0.30 / -0.03 / -0.00 / 0.16 / -0.35 / -0.48 / -0.04 / -0.05
69 / N.ar:O.co2 / 3.47 / -1.56 / -0.18 / 0.03 / -0.70 / -0.01 / -0.58 / -0.04 / -0.08 / -0.04 / 0.12 / 0.02 / 0.45 / 0.36 / 0.09 / 0.15
70 / N.ar:S.3 / 12.68 / 2.61 / 0.55 / 0.17 / -1.42 / -3.18 / -0.47 / -0.07 / -0.39 / -0.04 / -0.03 / -0.04 / -0.61 / 0.01 / 0.04 / 0.04
71 / N.ar:S.O2 / 101.44 / 26.16 / 0.53 / 0.58 / 0.04 / -0.30 / -0.71 / 0.16 / -1.65 / -0.00 / -1.15 / -1.02 / 1.60 / 0.07 / -2.63 / 0.18
72 / N.am:N.am / 5.70 / 0.88 / 0.68 / 0.57 / 0.31 / 0.20 / 0.04 / -0.02 / -0.05 / -0.09 / -0.01 / -0.05 / -0.05 / -0.19 / -0.02 / -0.01
73 / N.am:N.pl3 / 5.70 / 3.86 / 1.21 / 3.86 / 0.23 / 0.08 / -0.01 / -0.79 / -0.77 / -0.03 / -0.00 / -0.00 / -0.01 / -0.04 / -0.21 / -0.02
74 / N.am:O.3 / 6.94 / 0.89 / -0.16 / 0.08 / 0.22 / 0.06 / 0.68 / 0.15 / -0.40 / -0.00 / 0.05 / -0.01 / -0.02 / -0.03 / -0.03 / -0.06
75 / N.am:O.2 / 6.94 / 0.08 / -3.82 / 0.69 / 0.64 / 0.97 / 0.09 / 0.05 / -0.29 / 0.00 / 0.27 / 0.60 / 0.08 / -0.02 / -0.05 / -0.06
76 / N.am:O.co2 / 3.47 / 0.71 / -2.78 / 0.06 / 0.37 / 1.86 / 0.07 / 0.00 / -0.04 / -0.27 / -0.01 / -0.01 / -0.01 / -0.00 / -0.02 / -0.03
77 / N.am:S.3 / 12.68 / 0.59 / 3.23 / 5.63 / 0.13 / 0.00 / 0.89 / 0.07 / 2.86 / -0.00 / -0.02 / -0.55 / -0.03 / -0.05 / -0.05 / -0.07
78 / N.am:S.2 / 139.48 / 2.61 / 0.71 / 0.42 / 0.15 / -0.29 / 0.00 / 0.01 / 0.21 / 0.86 / -0.95 / -0.03 / -0.07 / 0.01 / -0.04 / -0.94
79 / N.am:S.O2 / 266.28 / 2.61 / 0.53 / 0.42 / 0.36 / -2.53 / -0.03 / 0.12 / 0.08 / -1.39 / -2.22 / -2.12 / -0.75 / 0.64 / -0.00 / -1.29
80 / N.am:P.3 / 15.72 / 3.32 / 3.66 / 0.67 / -0.83 / -3.75 / -0.64 / 0.32 / 3.13 / 0.66 / -0.01 / -0.06 / -0.05 / -0.00 / 0.80 / 0.24
81 / N.am:F / 10.45 / 2.17 / 0.23 / 0.05 / 0.09 / 0.07 / 0.08 / 0.02 / 0.02 / 0.39 / -0.01 / -0.04 / -0.10 / -0.04 / -0.40 / -0.04
82 / N.pl3:O.3 / 3.47 / 0.01 / -2.45 / 0.49 / -0.01 / 0.64 / 0.85 / -0.00 / -0.04 / -0.17 / -0.03 / 0.39 / 0.76 / 0.11 / 0.15 / 0.19
83 / N.pl3:O.2 / 6.94 / -0.06 / -2.70 / -0.28 / 1.10 / 0.85 / 0.10 / 0.18 / 0.00 / -0.33 / -0.02 / -0.01 / -0.25 / -0.01 / -0.01 / -0.02
84 / N.pl3:O.co2 / 6.94 / -5.19 / -3.52 / -0.12 / -0.19 / -0.06 / 0.71 / 0.03 / -0.08 / -0.05 / 0.05 / 0.27 / 0.09 / 0.11 / 0.92 / 0.78
85 / N.pl3:S.3 / 240.92 / 10.46 / 4.22 / 2.79 / 3.55 / -0.10 / -0.14 / -1.51 / 0.07 / 1.77 / -0.02 / -0.12 / -0.26 / 0.03 / 1.05 / -0.54
86 / N.pl3:P.3 / 15.72 / 6.64 / 0.52 / 0.20 / -3.17 / -3.65 / -1.20 / 1.55 / 0.10 / 0.04 / 0.02 / -0.10 / -0.02 / 1.04 / 1.69 / 1.21
87 / O.3:O.3 / 2.00 / -2.46 / 0.00 / 0.61 / 0.02 / 0.13 / -0.01 / -0.02 / -0.03 / -0.16 / 0.07 / 0.30 / 0.32 / 0.39 / -0.01 / -0.41
88 / O.3:O.2 / 6.02 / 0.08 / 0.19 / 0.30 / 0.05 / 0.05 / 0.97 / 0.04 / 0.14 / -0.27 / -0.00 / -0.01 / -0.02 / -0.03 / -0.04 / -0.06
89 / O.3:O.co2 / 2.00 / -1.67 / -0.11 / -1.00 / -0.62 / 0.09 / 0.04 / -0.00 / -0.11 / -0.00 / 0.16 / 0.63 / 0.12 / 0.04 / 0.03 / 0.02
90 / O.3:S.3 / 16.12 / 5.01 / 2.78 / 0.49 / 0.52 / -0.31 / -0.20 / -0.06 / -1.28 / -0.30 / -0.05 / -0.54 / 0.08 / 1.01 / 0.19 / -0.06
91 / O.3:P.3 / 10.20 / 8.27 / 3.26 / 0.02 / -4.17 / -2.19 / -0.51 / 1.79 / 0.10 / 0.78 / 0.01 / 1.22 / 0.75 / 0.16 / 0.40 / 1.28
92 / O.2:O.2 / 6.02 / 3.55 / 3.64 / 1.42 / 0.13 / 0.03 / 0.26 / 0.03 / -0.06 / -0.05 / 0.04 / 0.01 / -0.29 / -0.03 / -0.09 / -0.04
93 / O.2:O.co2 / 2.00 / 0.26 / 0.20 / 0.09 / 0.04 / 0.04 / 0.07 / 0.17 / -0.03 / -0.03 / -0.02 / -0.01 / -0.01 / -0.08 / -0.03 / -0.05
94 / O.2:S.3 / 8.06 / 12.36 / 9.03 / 0.09 / 0.50 / -0.00 / -0.00 / 0.10 / -0.38 / 0.01 / -0.01 / -0.18 / -0.03 / -0.01 / -0.02 / -0.69
95 / O.2:S.2 / 40.30 / 20.52 / 0.45 / 0.29 / 0.05 / 0.24 / 0.08 / -0.01 / 0.35 / -0.11 / -0.08 / -0.64 / -0.96 / 0.01 / -0.03 / -0.95
96 / O.2:S.O2 / 8.06 / 1.57 / 1.66 / 6.29 / 2.66 / 0.22 / 0.20 / 0.10 / -0.11 / 0.96 / -1.20 / 0.27 / -1.92 / -0.02 / -0.08 / -0.90
97 / O.2:P.3 / 20.40 / 4.13 / 5.32 / 2.36 / 0.40 / 0.28 / 0.34 / 0.06 / 0.04 / -0.48 / -0.54 / -0.08 / -0.54 / -0.05 / -0.02 / -0.03
98 / O.2:F / 9.34 / 7.84 / 0.18 / 0.03 / 0.07 / 0.04 / 0.02 / 0.05 / 0.99 / 0.01 / -0.10 / -0.27 / -0.03 / -0.32 / -0.27 / -0.48
99 / O.co2:O.co2 / 2.00 / 0.17 / 0.06 / -0.69 / 0.99 / 1.35 / 0.01 / -0.01 / -0.01 / -0.05 / -0.07 / -0.02 / -0.02 / -0.02 / 0.50 / 0.82
100 / O.co2:S.3 / 8.06 / 14.21 / 2.61 / -1.21 / -1.04 / -0.22 / 0.81 / -0.00 / -0.17 / -0.00 / 0.01 / -0.03 / 0.00 / -0.55 / -0.00 / -0.05
101 / O.co2:P.3 / 10.20 / 4.13 / 3.56 / 4.74 / 0.04 / -0.12 / -2.77 / -0.03 / -0.00 / 0.03 / -0.15 / -0.85 / 0.00 / -0.01 / -0.63 / -0.00

Table S3.The CASF-2013 benchmark of 195 protein-ligand complexes as well as their experimental binding constants and predicted binding affinities. The first column is the PDB ID; the second column is the protein name, in total there are 65 proteins, each has three complexes in each cluster; the third column is the experimental binding constant Ki or Kd; the fourth column is the experimental binding affinity calculated by RTln(ki)/4180, the unit is kcal/mol; The fifth column is the predicted binding affinity calculated by SPA 2.0, the fitting linear equation to the experimental binding affinities is y=-3.76+0.0371x, the unit is kcal/mol.

ID / Protein Name / Ki or Kd / GExp / GSPA
1PS3 / Alpha-Mannosidase II / 5.2mM / -3.110 / -7.157
3D4Z / Alpha-Mannosidase II / 13uM / -6.670 / -7.142
3EJR / Alpha-Mannosidase II / 2.7nM / -11.69 / -9.133
2QMJ / Maltase-Glucoamylase / 62uM / -5.743 / -8.179
3L4W / Maltase-Glucoamylase / 1.0uM / -8.184 / -7.442
3L4U / Maltase-Glucoamylase / 0.03uM / -10.25 / -7.898
3L7B / Glycogen Phosphorylase / 4.01mM / -3.273 / -7.443
3G2N / Glycogen Phosphorylase / 81uM / -5.579 / -7.503
3EBP / Glycogen Phosphorylase / 1.24uM / -8.062 / -8.507
2W66 / O-Glcnacase BT_4395 / 89uM / -5.524 / -7.181
2WCA / O-Glcnacase BT_4395 / 2.5uM / -7.639 / -7.606
2VVN / O-Glcnacase BT_4395 / 50nM / -9.958 / -8.302
2X97 / Angiotensin Converting Enzyme / 2200nM / -7.720 / -9.231
2XHM / Angiotensin Converting Enzyme / 0.16uM / -9.276 / -10.73
2X8Z / Angiotensin Converting Enzyme / 11nM / -10.85 / -7.228
2X0Y / O-Glcnacase NAGJ / 25uM / -6.275 / -7.730
2CBJ / O-Glcnacase NAGJ / 5.4nM / -11.28 / -7.946
2J62 / O-Glcnacase NAGJ / 4.6pM / -15.46 / -9.773
3BKK / Angiotensin Converting Enzyme / 0.83uM / -8.293 / -10.28
3L3N / Angiotensin Converting Enzyme / 6.6nM / -11.15 / -9.656
2XY9 / Angiotensin Converting Enzyme / 0.65nM / -12.53 / -12.81
1GPK / Acetylcholinesterase / 4.3uM / -7.325 / -7.454
1H23 / Acetylcholinesterase / 4.5nM / -11.39 / -11.59
1E66 / Acetylcholinesterase / 0.13nM / -13.49 / -9.602
3CJ2 / RNA-Dependent RNA Polymerase / 14uM / -6.616 / -7.403
2D3U / RNA-Dependent RNA Polymerase / 0.12uM / -9.439 / -10.33
3GNW / RNA-Dependent RNA Polymerase / 0.79nM / -12.41 / -10.98
3F3A / Transporter / 64.8uM / -5.715 / -7.522
3F3C / Transporter / 950nM / -8.212 / -7.555
3F3E / Transporter / 20nM / -10.50 / -6.914
4GQQ / Alpha-Amylase / 1.3mM / -3.942 / -5.989
1U33 / Alpha-Amylase / 25uM / -6.275 / -8.660
1XD0 / Alpha-Amylase / 0.075uM / -9.712 / -11.73
2WBG / Beta-Glucosidase / 35.2uM / -6.070 / -9.126
2J78 / Beta-Glucosidase / 384nM / -8.757 / -7.415
2CET / Beta-Glucosidase / 9.6nM / -10.94 / -9.054
2ZXD / Alpha-L-Fucosidase / 6.0uM / -7.120 / -7.540
2ZWZ / Alpha-L-Fucosidase / 16.3nM / -10.62 / -7.285
2ZX6 / Alpha-L-Fucosidase / 25.1pM / -14.45 / -9.098
3UDH / Beta-Secretase / 1.4mM / -3.887 / -6.914
4DJV / Beta-Secretase / 0.19uM / -9.166 / -8.951
4GID / Beta-Secretase / 0.017nM / -14.69 / -14.42
3FK1 / 3-Phosphoshikimate 1-Carboxyvinyltransferase / 2420uM / -3.574 / -5.605
2QFT / 3-Phosphoshikimate 1-Carboxyvinyltransferase / 5.5uM / -7.175 / -6.937
2PQ9 / 3-Phosphoshikimate 1-Carboxyvinyltransferase / 7.8nM / -11.06 / -9.976
1F8D / Neuraminidase / 400uM / -4.638 / -6.353
1F8B / Neuraminidase / 4.0uM / -7.366 / -6.319
1F8C / Neuraminidase / 0.04uM / -10.09 / -7.057
1N2V / QueuinetRNA-Ribosyltransferase / 83uM / -5.565 / -6.405
1R5Y / QueuinetRNA-Ribosyltransferase / 0.35uM / -8.812 / -8.399
3GE7 / QueuinetRNA-Ribosyltransferase / 2nM / -11.86 / -10.43
3HUC / Mitogen-Activated Protein Kinase / 1030nM / -8.171 / -9.489
3GCS / Mitogen-Activated Protein Kinase / 56nM / -9.889 / -11.04
3E93 / Mitogen-Activated Protein Kinase / 1.4nM / -12.07 / -12.15
1Q8T / cAMP-Dependent Protein Kinase / 17.5uM / -6.493 / -7.539
1Q8U / cAMP-Dependent Protein Kinase / 1.1uM / -8.130 / -8.564
3AG9 / cAMP-Dependent Protein Kinase / 9nM / -10.98 / -10.58
3OWJ / Casein Kinase II / 0.86uM / -8.280 / -7.687
2ZJW / Casein Kinase II / 0.02uM / -10.50 / -7.735
3PE2 / Casein Kinase II / 0.175nM / -13.31 / -9.467
2V00 / Endothiapepsin / 0.22mM / -4.992 / -6.733
3PWW / Endothiapepsin / 48nM / -9.985 / -11.95
3URI / Endothiapepsin / 1nM / -12.27 / -12.91
3MFV / Arginase-1 / 3000uM / -3.437 / -6.401
3F80 / Arginase-1 / 60uM / -5.756 / -5.937
3KV2 / Arginase-1 / 47.51nM / -9.985 / -5.557
2HB1 / Protein-Tyrosine Phosphatase / 160uM / -5.183 / -7.037
2QBR / Protein-Tyrosine Phosphatase / 0.47uM / -8.634 / -8.275
2QBP / Protein-Tyrosine Phosphatase / 0.004uM / -11.45 / -10.54
3FCQ / Thermolysin / 1.7mM / -3.778 / -5.726
1OS0 / Thermolysin / 0.93uM / -8.225 / -10.09
4TMN / Thermolysin / 0.068nM / -13.87 / -10.92
3PXF / Cell Division Protein Kinase / 37uM / -6.043 / -6.851
2XNB / Cell Division Protein Kinase / 149nM / -9.317 / -9.545
2FVD / Cell Division Protein Kinase / 3nM / -11.62 / -9.796
1QI0 / Endoglucanase / 4.5mM / -3.205 / -5.860
1W3K / Endoglucanase / 50uM / -5.865 / -6.914
1W3L / Endoglucanase / 0.52uM / -8.566 / -8.112
3IMC / PantothenateSynthetase / 1100uM / -4.037 / -6.801
3IVG / PantothenateSynthetase / 50uM / -5.865 / -9.682
3COY / PantothenateSynthetase / 0.96uM / -8.212 / -10.95
3B3S / LeucylAminopeptidase / 2800uM / -3.478 / -5.972
3B3W / LeucylAminopeptidase / 65uM / -5.715 / -5.887
3VH9 / LeucylAminopeptidase / 0.58uM / -8.512 / -6.568
3MSS / Tyrosine-Protein Kinase ABL1 / 22uM / -6.356 / -7.519
3K5V / Tyrosine-Protein Kinase ABL1 / 0.5uM / -8.594 / -9.048
2V7A / Tyrosine-Protein Kinase ABL1 / 0.005uM / -11.32 / -9.057
2BRB / Serine/Threonine-Protein Kinase Chk1 / 13.7uM / -6.629 / -7.859
3JVS / Serine/Threonine-Protein Kinase Chk1 / 0.29uM / -8.921 / -7.715
1NVQ / Serine/Threonine-Protein Kinase Chk1 / 5.6nM / -11.25 / -9.917
3ACW / Dehydrosqualene Synthase / 17.5uM / -6.493 / -9.367
2ZCR / Dehydrosqualene Synthase / 135nM / -9.371 / -8.547
2ZCQ / Dehydrosqualene Synthase / 1.5nM / -12.03 / -8.759
1BCU / Thrombin / 0.53mM / -4.474 / -6.692
1OYT / Thrombin / 0.057uM / -9.876 / -10.55
3UTU / Thrombin / 0.012nM / -14.89 / -12.35
3U9Q / Peroxisome Proliferator-Activated Receptor γ / 41.7uM / -5.974 / -7.725
2YFE / Peroxisome Proliferator-Activated Receptor γ / 0.236uM / -9.044 / -8.470
2P4Y / Peroxisome Proliferator-Activated Receptor γ / 1nM / -12.27 / -12.25
3UO4 / Serine/Threonine-Protein Kinase / 299nM / -8.894 / -9.135
2WTV / Serine/Threonine-Protein Kinase / 1.8nM / -11.92 / -10.51
3MYG / Serine/Threonine-Protein Kinase / 0.02nM / -14.59 / -8.771
3KGP / Urokinase-Type Plasminogen Activator / 2.68mM / -3.505 / -5.637
1O5B / Urokinase-Type Plasminogen Activator / 1.7uM / -7.871 / -6.997
1SQA / Urokinase-Type Plasminogen Activator / 0.62nM / -12.56 / -9.299
3KWA / Carbonic Anhydrase II / 84uM / -5.565 / -5.552
2WEG / Carbonic Anhydrase II / 314nM / -8.866 / -9.192
3DD0 / Carbonic Anhydrase II / 1nM / -12.27 / -10.04
2XDL / Heat Shock Protein Hsp90-Alpha / 790uM / -4.228 / -6.867
1YC1 / Heat Shock Protein Hsp90-Alpha / 680nM / -8.416 / -7.630
2YKI / Heat Shock Protein Hsp90-Alpha / 0.35nM / -12.90 / -12.30
1P1Q / Glutamate Receptor 2 / 12.8uM / -6.670 / -7.186
3BFU / Glutamate Receptor 2 / 531nM / -8.553 / -7.832
4G8M / Glutamate Receptor 2 / 12.8nM / -10.76 / -8.465
3G2Z / Beta-Lactamase / 4.4mM / -3.219 / -5.900
4DE2 / Beta-Lactamase / 76.0uM / -5.620 / -7.923
4DE1 / Beta-Lactamase / 1.1uM / -8.130 / -7.410
1VSO / Glutamate Receptor, IonotropicKainate 1 / 18.98uM / -6.438 / -7.964
3GBB / Glutamate Receptor, IonotropicKainate 1 / 126nM / -9.412 / -9.397
3FV1 / Glutamate Receptor, IonotropicKainate 1 / 0.5nM / -12.68 / -10.07
2Y5H / Coagulation Factor X / 1620nM / -7.898 / -9.817
2XBV / Coagulation Factor X / 3.7nM / -11.49 / -11.55
1MQ6 / Coagulation Factor X / 7pM / -15.21 / -10.12
1LOQ / Orotidine 5'-Monophosphate Decarboxylase / 0.2mM / -5.047 / -7.878
1LOL / Orotidine 5'-Monophosphate Decarboxylase / 0.41uM / -8.716 / -7.947
1LOR / Orotidine 5'-Monophosphate Decarboxylase / 8.8pM / -15.08 / -8.705
1UTO / Trypsin Beta / 5.32mM / -3.096 / -5.720
3GY4 / Trypsin Beta / 8uM / -6.957 / -6.893
1O3F / Trypsin Beta / 0.011uM / -10.85 / -8.611
2YGE / Heat Shock Protein HSP82 / 8.62uM / -6.902 / -8.486
2IWX / Heat Shock Protein HSP82 / 0.21uM / -9.112 / -7.381
2VW5 / Heat Shock Protein HSP82 / 3nM / -11.62 / -8.651
2YMD / Acetylcholine Receptor / 693uM / -4.310 / -8.684
2XYS / Acetylcholine Receptor / 38nM / -10.12 / -8.950
2X00 / Acetylcholine Receptor / 4.7pM / -15.45 / -10.37
2R23 / Antibody FAB fragment / 190uM / -5.074 / -5.762
3BPC / Antibody FAB fragment / 16uM / -6.547 / -6.178
1KEL / Antibody FAB fragment / 52nM / -9.930 / -8.980
3OZT / Catechol O-methyltransferase / 74.9uM / -5.633 / -9.983
3OE5 / Catechol O-methyltransferase / 132nM / -9.385 / -10.67
3NW9 / Catechol O-methyltransferase / 1nM / -12.27 / -11.00
1ZEA / Antibody FAB Fragment / 6uM / -7.120 / -8.996
2PCP / Antibody FAB Fragment / 2nM / -11.86 / -8.473
1IGJ / Antibody FAB Fragment / 0.1nM / -13.64 / -8.737
1LBK / Glutathione S-Transferase P1-1 / 668uM / -4.337 / -7.332
2GSS / Glutathione S-Transferase P1-1 / 11.5uM / -6.738 / -6.535
10GS / Glutathione S-Transferase P1-1 / 0.4uM / -8.730 / -9.091
3SU5 / NS3/4A Protease / 2635nM / -7.611 / -12.05
3SU2 / NS3/4A Protease / 44.8nM / -10.02 / -12.05
3SU3 / NS3/4A Protease / 0.74nM / -12.45 / -12.08
3N7A / 3-Dehydroquinate Dehydratase / 200uM / -5.047 / -6.647
3N86 / 3-Dehydroquinate Dehydratase / 2.3uM / -7.693 / -9.367
2XB8 / 3-Dehydroquinate Dehydratase / 26nM / -10.35 / -8.675
3AO4 / HIV-1 Integrase / 8.5mM / -2.823 / -6.339
3ZSX / HIV-1 Integrase / 519uM / -4.474 / -8.175
3ZSO / HIV-1 Integrase / 7.6uM / -6.984 / -8.934
3NQ3 / Beta-Lactoglobulin / 167uM / -5.156 / -6.782
3UEU / Beta-Lactoglobulin / 5.81uM / -7.148 / -6.977
3UEX / Beta-Lactoglobulin / 0.12uM / -9.439 / -8.633
3LKA / Macrophage Metalloelastase (MMP-12) / 1.5mM / -3.846 / -7.298
3EHY / Macrophage Metalloelastase (MMP-12) / 1.4uM / -7.980 / -8.097
3F17 / Macrophage Metalloelastase (MMP-12) / 2.36nM / -11.77 / -9.831
3CFT / Transthyretin / 64uM / -5.715 / -7.072
4DES / Transthyretin / 1.40uM / -7.980 / -6.639
4DEW / Transthyretin / 0.10uM / -9.548 / -3.881
3DXG / Ribonuclease Pancreatic / 4.0mM / -3.273 / -6.059
1W4O / Ribonuclease Pancreatic / 6uM / -7.120 / -6.868
1U1B / Ribonuclease Pancreatic / 16nM / -10.64 / -8.769
3OV1 / Growth factor receptor-bound protein 2 / 6.25uM / -7.093 / -9.416
3S8O / Growth factor receptor-bound protein 2 / 0.14uM / -9.344 / -9.979
1JYQ / Growth factor receptor-bound protein 2 / 2nM / -11.86 / -11.46
1A30 / HIV-1 Protease / 50uM / -5.865 / -8.434
3CYX / HIV-1 Protease / 10nM / -10.91 / -13.16
4DJR / HIV-1 Protease / 0.003nM / -15.71 / -12.45
3I3B / Beta-Galactosidas / 5.9mM / -3.042 / -6.299
3MUZ / Beta-Galactosidas / 0.35mM / -4.719 / -6.984
3VD4 / Beta-Galactosidas / 0.015mM / -6.575 / -6.991
2VO5 / Beta-Mannosidase / 13uM / -6.670 / -9.117
2VL4 / Beta-Mannosidase / 975nM / -8.198 / -7.496
2VOT / Beta-Mannosidase / 72nM / -9.739 / -8.556
1N1M / Dipeptidyl Peptidase 4 / 2uM / -7.775 / -5.721
2OLE / Dipeptidyl Peptidase 4 / 56.2nM / -9.889 / -7.043
3NOX / Dipeptidyl Peptidase 4 / 2.2nM / -11.81 / -7.682
1HNN / Phenylethanolamine N-Methyltransferase / 0.58uM / -8.512 / -8.231
2G70 / Phenylethanolamine N-Methyltransferase / 17nM / -10.59 / -8.039
2OBF / Phenylethanolamine N-Methyltransferase / 1.4nM / -12.07 / -11.03
1Z95 / Androgen receptor / 76nM / -9.712 / -13.77
3B68 / Androgen receptor / 4nM / -11.45 / -11.91
3G0W / Androgen receptor / 0.3nM / -12.98 / -11.77
1SLN / Stromelysin-1 / 0.23uM / -9.057 / -10.50
2D1O / Stromelysin-1 / 0.02uM / -10.50 / -9.970
1HFS / Stromelysin-1 / 2nM / -11.86 / -16.41
2JDY / Fucose-Binding Lectin PA-II / 42.9uM / -5.961 / -5.540
2JDM / Fucose-Binding Lectin PA-II / 3.96uM / -7.366 / -5.548
2JDU / Fucose-Binding Lectin PA-II / 0.19uM / -9.166 / -5.423

Table S4. Success Rate of Identifying the “Native” Pose with/without the Inclusion of the “Native” Pose for the Docking Power Test

Scoring Functiona / Success Rate (%)
With “Native” Pose / Without “Native” Pose
SPA 2.0 / 82.1 / 76.4
SPA 1.0 / 81.0 / 75.9
ChemPLP@GOLD / 81.0 / 79.5
ChemScore@Gold / 77.9 / 76.9
GlideScore-SP / 78.5 / 74.4
ASP@Gold / 71.8 / 69.7
LigScore2@DS / 76.9 / 71.8
PLP1@DS / 77.4 / 73.8
Alpha-HP@MOE / 75.4 / 73.8
PMF / 74.9 / 69.2
GlideScore-XP / 74.4 / 70.8
GoldScore@Gold / 71.3 / 70.8
LUDI1@DS / 59.0 / 57.9
Affinity-dG@MOE / 63.1 / 60.5
ChemScore@SYBYL / 59.5 / 59.5
London-dG@MOE / 59.5 / 57.4
X-ScoreHM / 61.0 / 59.5
G-Score@SYBYL / 45.1 / 44.6
Jain@DS / 48.2 / 48.2
PMF@SYBYL / 51.8 / 41.5
PMF04@DS / 51.8 / 49.2
ASE@MOE / 51.3 / 49.7
D-Score@SYBYL / 18.5 / 18.5
aThe Results except SPA and PMF are extract from the literature [1].

Reference

  1. Li, Y.; Han, L.; Liu, Z.; Wang, R. Comparative Assessment of Scoring Functions on an Updated Benchmark: II. Evaluation Methods and General Results.J.Chem.Info.Mod.2014, 54,1717–1736.