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.
	\(\theta_{\text{ACC}\_\text{LP}}\)	0°	20°	60°	From [RiboDock2004] Figure 2.
	\(\phi_{\text{ACC}\_\text{PLANE}}\)	0°	60°	75°	From [RiboDock2004] Figure 2.
	\(\theta_{\text{ACC}\_\text{PLANE}}\)	0°	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.
	\(\alpha_{\text{slip}}\)	0°	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