Appendix

Table 21 Van der Waals parameters in Tripos 5.2 force field (R = radius (Å); K = well depth (kcal/mol); IP = Ionization potential (eV); POL = polarisability (1025 cm3)).

Atom Type

R

K

IP

POL

Description

H

1.5

0.042

13.6

4

Non-polar hydrogen

H.P

1.2

0.042

13.6

4

Polar hydrogen

C.3

1.7

0.107

14.61

13.8

C sp3 (0 implicit H)

C.3.H1

1.8

0.107

14.61

16.38

C sp3 (1 implicit H)

C.3.H2

1.9

0.107

14.61

19.27

C sp3 (2 implicit H)

C.3.H3

2

0.107

14.61

22.47

C sp3 (3 implicit H)

C.2

1.7

0.107

15.62

13.8

C sp2 (0 implicit H)

C.cat

1.7

0.107

15.62

13.8

C sp2 (guanidinium centre)

C.2.H1

1.8

0.107

15.62

16.38

C sp2 (1 implicit H)

C.2.H2

1.9

0.107

15.62

19.27

C sp2 (2 implicit H)

C.ar

1.7

0.107

15.62

13.8

C aromatic (0 implicit H)

C.ar.H1

1.8

0.107

15.62

16.38

C aromatic (1 implicit H)

C.1

1.7

0.107

17.47

13.8

C sp (0 implicit H)

C.1.H1

1.8

0.107

17.47

16.38

C sp (1 implicit H)

N.4

1.55

0.095

33.29

8.4

N sp3+ (cationic)

N.3

1.55

0.095

18.93

8.4

N sp3

N.pl3

1.55

0.095

19.72

8.4

N trigonal planar (non-amide)

N.am

1.55

0.095

19.72

8.4

N trigonal planar (amide)

N.2

1.55

0.095

22.1

8.4

N sp2

N.ar

1.55

0.095

22.1

8.4

N aromatic

N.1

1.55

0.095

23.91

8.4

N sp

O.3

1.52

0.116

24.39

5.4

O sp3

O.2

1.52

0.116

26.65

5.4

O sp2

O.co2

1.52

0.116

35.12

5.4

O carboxylate

S.3

1.8

0.314

15.5

29.4

S sp3

S.o

1.7

0.314

15.5

29.4

sulfoxide

S.o2

1.7

0.314

15.5

29.4

sulfone

S.2

1.8

0.314

17.78

29.4

S sp2

P.3

1.8

0.314

16.78

40.6

F

1.47

0.109

20.86

3.7

Cl

1.75

0.314

15.03

21.8

Br

1.85

0.434

13.1

31.2

I

1.98

0.623

12.67

49

Na

1.2

0.4

K

1.2

0.4

UNDEFINED

1.2

0.042

Table 22 Geometrical parameters for empirical terms (a = Geometric variable; b = Ideal value; c = Tolerance on ideal value; d = Deviation at which score is reduced to zero).

Term

\(X\)a

\(X_0\)b

\(X_{\min}\)c

\(X_{\max}\)d

Description

\(S_{\text{polar}}\)

\(R_{12}\)

\(R\) + 0.05 Å

0.25 Å

0.6 Å

Distance between interaction centres

\(\alpha_{\text{DON}}\)

180°

30°

80°

Angle around donor H

\(\alpha_{\text{ACC}}\)

180°

60°

100°

Angle around acceptor

\(\alpha_{\text{C+}}\)

180°

60°

100°

Angle between C+ACC vector and normal to plane of guanidinium group

\(\phi_{\text{ACC}\_\text{LP}}\)

45°

15°

15°

From [RiboDock2004] Figure 2.

\(\theta_{\text{ACC}\_\text{LP}}\)

20°

60°

From [RiboDock2004] Figure 2.

\(\phi_{\text{ACC}\_\text{PLANE}}\)

60°

75°

From [RiboDock2004] Figure 2.

\(\theta_{\text{ACC}\_\text{PLANE}}\)

20°

60°

From [RiboDock2004] Figure 2.

\(S_{\text{repul}}\)

\(R_{12}\)

R + 1.1 Å

0.25 Å

0.6 Å

Distance between interaction centres

\(\alpha_{\text{DON}}\)

180°

30°

60°

Angle around donor H

\(\alpha_{\text{ACC}}\)

180°

30°

60°

Angle around acceptor

\(S_{\text{arom}}\)

\(R_{\text{perp}}\)

3.5 Å

0.25 Å

0.6 Å

From [RiboDock2004] Figure 3.

\(\alpha_{\text{slip}}\)

20°

60°

From [RiboDock2004] Figure 3.

Table 23 Angular functions used to describe attractive and repulsive polar interactions (a = Interaction centre types; b = angular functions in equations (6)(13)).

\(\text{IC1}\)a

\(\text{ANG}_{\text{IC1}}\)b

\(\text{IC2}\)a

\(\text{ANG}_{\text{IC2}}\)b

Attractive (\(S_{\text{polar}}\))

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

ACC_LP

\(f_1(|\Delta\phi_{\text{ACC}\_\text{LP}}|) \cdot f_1(|\Delta\theta_{\text{ACC}\_\text{LP}}|)\)

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

ACC_PLANE

\(f_1(|\Delta\phi_{\text{ACC}\_\text{PLANE}}|) \cdot f_1(|\Delta\theta_{\text{ACC}\_\text{PLANE}}|)\)

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

ACC

\(f_1(|\Delta\alpha_{\text{ACC}}|)\)

M+

1

ACC_LP

\(f_1(|\Delta\phi_{\text{ACC}\_\text{LP}}|) \cdot f_1(|\Delta\theta_{\text{ACC}\_\text{LP}}|)\)

M+

1

ACC_PLANE

\(f_1(|\Delta\phi_{\text{ACC}\_\text{PLANE}}|) \cdot f_1(|\Delta\theta_{\text{ACC}\_\text{PLANE}}|)\)

M+

1

ACC

\(f_1(|\Delta\alpha_{\text{ACC}}|)\)

1

ACC_LP

C+

\(f_1(|\Delta\alpha_{\text{C+}}|)\)

ACC_PLANE

\(f_1(|\Delta\alpha_{\text{ACC}}|)\)

1

ACC

Repulsive (\(S_{\text{repul}}\))

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

M+

1

DON

\(f_1(|\Delta\alpha_{\text{DON}}|)\)

C+

1

M+

1

C+

1

C+

1

C+

1

ACC_LP

ACC_LP

ACC_PLANE

\(f_1(|\Delta\alpha_{\text{ACC}}|)\)

ACC_PLANE

\(f_1(|\Delta\alpha_{\text{ACC}}|)\)

ACC

ACC

Table 24 Solvation parameters (a = Frequency of occurrence in training set).

Atom type

Description

\(N\)a

\(r_i\)

\(p_i\)

\(w_i\)

C_sp3

Apolar carbon sp3 with 0 implicit H

48

1.7

2.149

0.8438

CH_sp3

Apolar carbon sp3 with 1 implicit H

59

1.8

1.276

0.0114

CH2_sp3

Apolar carbon sp3 with 2 implicit H

487

1.9

1.045

0.0046

CH3_sp3

Apolar carbon sp3 with 3 implicit H

409

2

0.88

0.0064

C_sp2

Apolar carbon sp2 with 0 implicit H

10

1.72

1.554

0.0789

CH_sp2

Apolar carbon sp2 with 1 implicit H

45

1.8

1.073

-0.0014

CH2_sp2

Apolar carbon sp2 with 2 implicit H

26

1.8

0.961

0.0095

C_sp2p

Positive charged carbon sp2

2

1.72

1.554

-0.7919

C_ar

Apolar aromatic carbon with 0 implicit H

116

1.72

1.554

0.017

CH_ar

Apolar aromatic carbon with 1 implicit H

357

1.8

1.073

-0.0143

C_sp

Carbon sp

24

1.78

0.737

-0.0052

C_sp3_P

Polar carbon sp3 with 0 implicit H

6

1.7

2.149

-0.0473

CH_sp3_P

Polar carbon sp3 with 1 implicit H

22

1.8

1.276

-0.0394

CH2_sp3_P

Polar carbon sp3 with 2 implicit H

130

1.9

1.045

-0.0078

CH3_sp3_P

Polar carbon sp3 with 3 implicit H

69

2

0.88

0.0033

C_sp2_P

Polar carbon sp2 with 0 implicit H

57

1.72

1.554

-0.2609

CH_sp2_P

Polar carbon sp2 with 1 implicit H

30

1.8

0.961

-0.005

CH2_sp2_P

Polar carbon sp2 with 2 implicit H

1

1.8

0.961

0.0095

C_ar_P

Polar aromatic carbon with 0 implicit H

53

1.72

1.554

-0.2609

CH_ar_P

Polar aromatic carbon with 1 implicit H

34

1.8

1.073

-0.0015

H

Explicit apolar hydrogen (not used)

0

1.2

1

0

HO

Polar hydrogen bonded to O

54

1

0.944

0.0499

HN

Polar hydrogen bonded to N

54

1.1

1.128

-0.0242

HNp

Positively charged polar hydrogen bonded to N

23

1.2

1.049

-1.9513

HS

Polar hydrogen bonded to S

4

1.2

0.928

0.0487

O_sp3

Ether oxygen

31

1.52

1.08

-0.138

OH_sp3

Alcohol/phenol oxygen

48

1.52

1.08

-0.272

O_tri

Ester oxygen

59

1.52

1.08

0.0965

OH_tri

Acid oxygen (neutral)

6

1.52

1.08

-0.0985

O_sp2

Oxygen sp2

83

1.5

0.926

-0.1122

ON

Nitro group oxygen

18

1.5

0.926

-0.0055

Om

Negatively charged oxygen (carboxylate etc.)

7

1.7

0.922

-0.717

N_sp3

Nitrogen sp3 with 0 attached H

8

1.6

1.215

-0.6249

NH_sp3

Nitrogen sp3 with 1 attached H

11

1.6

1.215

-0.396

NH2_sp3

Nitrogen sp3 with 2 attached H

11

1.6

1.215

-0.215

N_sp3p

Nitrogen sp3+

6

1.6

1.215

-0.1186

N_tri

Amide nitrogen with 0 attached H

15

1.55

1.028

-0.23

NH_tri

Amide nitrogen with 1 attached H

8

1.55

1.028

-0.4149

NH2_tri

Amide nitrogen with 2 attached H

6

1.55

1.028

-0.1943

N_sp2

Nitrogen sp2

3

1.55

1.413

-0.0768

N_sp2p

Nitrogen sp2+

5

1.55

1.413

-0.2744

N_ar

Aromatic nitrogen

26

1.55

1.413

-0.531

N_sp

Nitrogen sp

6

1.55

1

-0.1208

S_sp3

Sulphur sp3

15

1.8

1.121

-0.0685

S_sp2

Sulphur sp2

5

1.8

1.121

-0.0314

P

Phosphorous

10

1.8

1.589

-1.275

F

Fluorine

99

1.47

0.906

0.0043

Cl

Chlorine

132

1.75

0.906

-0.0096

Br

Bromine

37

1.85

0.898

-0.0194

I

Iodine

9

1.98

0.876

-0.0189

Metal

All metals

0

0.7

1

-1.6667

UNDEFINED

Undefined types

0

1.2

1

0