Table 1. The appearing frequencies of eight types of atomic probes in twenty types of natural amino acids as well as the values of its MCI, VWI and MHI

No. / Probe / Frequency / MCI / VWI / MHI
1 / H / 197 / 0.227 / 1.200 / -6.384E-3
2 / C(sp3) / 59 / -0.220 / 1.700 / -8.527E-1
3 / C(sp2) / 48 / 0.296 / 1.615 / 3.035E-2
4 / N(sp3) / 25 / -0.714 / 1.550 / 4.006E-1
5 / N(sp2) / 4 / -0.592 / 1.473 / -8.931E-2
6 / O(sp3) / 25 / -0.578 / 1.520 / 1.347E-3
7 / O(sp2) / 24 / -0.470 / 1.444 / -5.602E-2
8 / S(sp3) / 2 / 0.011 / 1.800 / 7.618E-2

Table 2. Lennard-Jones atomic potential well parameter

Atom / ei(kJ/mol)0.5
H / 0.3985
C, S, most others / 0.5555
C(sp2) / 0.3966
N / 1.3142
O / 0.8789

Table 3. Van der Waals’radius and SASA for atoms in organic molecules

Atom / van der Waals’radius (10-1nm) / SASA(10-2nm2)
H / 1.20 / 84.85
C / 1.85 / 132.73
N / 1.54 / 108.62
P / 1.90 / 136.85
O / 1.40 / 98.52
S / 1.85 / 132.73
F / 1.35 / 94.34
Cl / 1.81 / 129.49
Br / 1.95 / 141.03
I / 2.15 / 158.37

Table 4. Atom types and their ASP values

No / Atom typea / ASPb
Hydrogen in
1 / COOH / -8.80E-04
2 / A–COOH(A has π electrons) / 7.06E-03
3 / S–H / 7.05E-03
4 / C.ar–N.am–H / 1.81E-03
5 / X–N.am–H(N.am is π affected) / -7.08E-03
6 / N.am–H(N.am is π affected) / 9.49E-04
7 / X–N.am–H / -7.85E-03
8 / N.am–H / -6.59E-03
9 / N+–H(charged N) / -1.92E-02
10 / C.ar–N–H / -5.01E-03
11 / X–N–H(N is π affected) / -1.22E-02
12 / N–H(N is π affected) / -3.15E-03
13 / X–N–H / -7.90E-03
14 / N–H / -8.41E-03
15 / C.ar–O–H / -2.18E-03
16 / X–O–H(N is π affected) / -4.46E-03
17 / O–H(N is π affected) / -2.11E-02
18 / X–O–H / -4.81E-03
19 / O–H / -8.92E-03
20 / X–C.ar–H / 6.52E-03
21 / C.ar–H(C.ar is hydrophobic carbonc) / 5.89E-03
22 / C.ar–H / 7.88E-03
23 / X–A–H(A has π electrons) / 6.14E-03
24 / A–H(A has π electrons and is hydrophobic carbon) / 9.41E-03
25 / A–H(A has π electrons) / 2.98E-03
26 / O-–H(charged O) / -2.80E-03
27 / X–C–H(C is π affected) / 3.39E-03
28 / C–H(C is π affected and is hydrophobic carbon) / 1.01E-02
29 / C–H(C is π affected) / 4.52E-03
30 / X–C–H / 2.93E-03
31 / C–H(C is hydrophobic carbon) / 1.23E-02
32 / C–H / 6.77E-03
sp3 oxygen in
33 / S–O / -3.92E-02
34 / P–O / 2.02E-02
35 / X–O(O is π affected) / 2.88E-02
36 / X–O / -9.03E-03
37 / C.ar–O / 1.15E-02
38 / R–O(O is π affected and is in acid) / 3.16E-03
39 / R–O(O is π affected) / 2.30E-02
40 / R–O / -1.82E-02
41 / O-(charged O, “O.co2” in Tripos force field) / -1.81E-02
sp2 oxygen in
42 / N–C=O(C is π affected) / -2.56E-02
43 / O–C=O(C is π affected) / 3.92E-03
44 / C=O(C is π affected) / -6.56E-03
45 / S=O(S is π affected) / -5.41E-03
46 / P=O / -3.73E-02
47 / N=O(N is π affected) / 6.60E-03
48 / N–C=O / -1.40E-02
49 / O–C=O / -1.05E-02
50 / C=O / -1.20E-02
51 / S=O / -8.90E-03
52 / N=O / 1.36E-03
sp3 carbon in
53 / S.o2–C / nde
54 / P–C / nde
55 / C.ar–C–X / nde
56 / A–C(A has π electrons) / nde
57 / X–C / nde
58 / C.ar–C(C is hydrophobic carbon) / nde
59 / C.ar–C / nde
60 / R–C(R has π electrons and C is hydrophobic carbon) / nde
61 / R–C(R has π electrons) / nde
62 / R–C(C is hydrophobic carbon) / -0.20
63 / R–C / -0.10
64 / O-–C–C–N+ / nde
65 / O-–C–C–N(Cα in amino acid) / nde
66 / C-(charged C, “C.cat” in Tripos force field) / nde
sp2 carbon in
67 / X(2) –C=X / 2.77E-02
68 / N–C=O(C is π affected) / 5.57E-02
69 / O–C=O(C is π affected) / -3.23E-02
70 / C=O(C is π affected) / 6.89E-03
71 / N–C=O / -8.63E-03
72 / O–C=O / 2.24E-02
73 / C=O / 8.04E-02
74 / X–C=N / -3.97E-02
75 / R–C=N / -1.76E-02
76 / X(2)–C=C / -3.98E-03
77 / N–C=C / -1.22E-02
78 / O–C=C / -4.29E-03
79 / C=C(C is hydrophobic carbon) / 1.28E-02
80 / C=C / 2.59E-02
sp carbon in
81 / X–C or X=C or X≡C / 7.75E-02
82 / R–C / 1.89E-03
Aromatic carbon in
83 / N.ar…C.ar–N / 2.24E-02
84 / N.ar… C.ar–O / 3.37E-02
85 / N.ar…C.ar / -9.39E-03
86 / C.ar–N / -7.99E-03
87 / C.ar–O / 5.64E-03
88 / C.ar–S.o2 / -9.75E-02
89 / R–C.ar(C.ar is hydrophobic carbon) / 3.62E-02
90 / R–C.ar / 2.13E-02
sp3 nitrogen in
91 / S–N / 8.81E-03
92 / P–N / -1.60E-02
93 / N–X (N is π affected) / -1.71E-02
94 / N–R (N is π affected) / 8.00E-03
95 / N–X / 5.29E-02
96 / N–R / 2.22E-02
97 / S(P)–N.pl3d / nde
98 / N.2(or N.am)ON.pl3 / 0.54
99 / X–N.pl3 / -0.15
100 / R–N.pl3 / 7.16E-02
101 / C.ar–N.pl3=O / -1.57E-02
102 / N.pl3=O / -4.28E-02
103 / N-(charged N, “N.4” in Tripos force field) / nde
sp2 nitrogen in
104 / X–N=O(N is π affected) / -8.11E-02
105 / X–N=O / -2.16E-02
106 / N=O / -9.44E-04
107 / X–N=N(N is π affected) / -1.91E-02
108 / X–N=N / -5.30E-02
109 / N=N(N is π affected) / 1.30E-02
110 / N=N / 4.69E-03
111 / N=C (N is π affected) / 3.05E-03
112 / N=C / -1.51E-02
sp nitrogen in
113 / A≡N / -1.95E-02
Amide nitrogen in
114 / X–N.am(N.am is π affected) / 0.39
115 / X–N.am / 1.99E-02
116 / R–N.am(N.am is π affected) / 7.53E-02
117 / R–N.am / 0.11
Aromatic nitrogen in
118 / N.ar / 1.30E-02
sp3 surfur in
119 / A–S.3(S.3 is π affected) / 1.64E-02
120 / A–S.3 / 1.04E-02
Sulfoxide sulfur in
121 / A–SO–A / -7.71E-02
122 / A–SO2–A / 0.53
Phosphorus in
123 / A–P / nde
sp2 sulfur in
124 / S=P / 2.02E-02
125 / S=A / 1.15E-03
Fluorine in
126 / A–F(A has π electrons) / 1.01E-02
127 / A–F / 1.28E-02
Chlorine in
128 / A–Cl(A has π electrons) / 1.53E-02
129 / A–Cl / 1.30E-02
Bromine in
130 / A–Br(A has π electrons) / 1.59E-02
131 / A–Br / 1.52E-02
Iodine in
132 / A–I(A has π electrons) / 1.69E-02
133 / A–I / 1.50E-02

adefinitions: … : aromatic bond; –: single bond; =: double bond; ≡: triple bond; X: N or O; R: any atom except X; A: any atom except hydrogen; π affected: at least one connected atom has π electrons; has π electrons: the atom itself is in π system (connected with at least one other atom with double or triple or aromatic bond).

bASP: atomic solvation parameter; unit is kJ/nm2 for ASP with all values multiplied by 568.48, or kcal/Ǻ2 for ASP with all values multiplied by 1.36, or kJ/Ǻ2 for ASP with all values multiplied by 5.6848.

chydrophobic carbon atom is sp3 or sp2 hybridized carbon atom if there is no hetero atom (any atom other than carbon) within the 1–4 relationship.

dthis is a special atom type adopted by the Tripos force field; A nitrogen is N.pl3 if it is connected with one or more atoms with π electrons and adopts a trigonal planar geometric structure instead of a tetrahedron.

end: not determined.

Table 5. The discriminant function for hydrophobic interaction in HINT

Atom type / H (apolar) / H (polar) / C (apolar) / polar (N,O,etc.)
H (apolar) / +1a / -1b / +1a / -1b
H (polar) / -1b / -1c / -1b / +1d
C (apolar) / +1a / -1b / +1a / -1b
polar (N,O,etc.) / -1b / +1d / -1b / -1e

ahydrophobic-hydrophobic.

bhydrophobic-polar.
cacid-acid (two polar hydrogens).
dacid-base or hydrogen bond.

emay depend on charge, but probably base-base and unfavorable (Tij=-1).

Table 6. Ten types of atoms according to element periodic tables

No / 1 / 2 / 3 / 4 / 5 / 6 / 7 / 8 / 9 / 10
Atom
types / H / C(sp3) / C(sp2) / C(sp) / N(sp3),P(sp3) / N(sp2),P(sp2) / N(sp),P(sp) / O(sp3),S(sp3) / O(sp2), S(sp2) / F,Cl,
Br, I

1