In silico screening of mutational effects on enzyme-proteic inhibitor affinity: a docking-based approach

BMC Structural Biology

Table 1 Human Ribonuclease Inhibitor (hRI) – Angiogenin (Ang) interaction: thermodynamic and kinetic data and ZD scores

hRI	Ang	log k_d^a	log k_a^b	ΔG°^c (kcal/mol)	ΔΔG^d(kcal/mol)	N_sol ^e	Best Rank^f	ZD_best^g	ZD-s^h	ZD_scⁱ	ZD_el^l	ZD_des^m
Wtⁿ	wt	-6.96	8.30	-20.8	-	43	1	82.4	64.2	47.0	17.1	0.1
des (S460)^n,o	R5A	-3.80	7.72	-15.7	5.1	38	3	74.5	61.0	45.1	14.7	1.2
des (S460)ⁿ	K40G	-3.14	7.87	-15.0	5.8	38	1	74.8	58.8	44.5	13.5	0.8
Q430A/V432Aⁿ	wt	-7.08	8.15	-20.8	0.1	45	1	81.7	63.1	46.0	17.1	0.0
W438A/S439A/E440Aⁿ	wt	-5.77	8.11	-18.9	1.9	45	1	81.8	63.9	45.9	17.3	0.6
R457Aⁿ	wt	-7.24	8.18	-21.0	-0.2	46	1	82.2	63.6	46.4	17.0	0.2
I459Aⁿ	wt	-6.70	8.08	-20.2	0.7	47	1	82.0	63.1	46.0	17.3	-0.2
wtⁿ	H84A	-6.85	8.28	-20.6	0.2	41	1	80.4	63.9	46.7	17.1	0.1
wtⁿ	W89A	-6.80	8.30	-20.6	0.2	44	1	78.7	61.1	44.4	17.4	-0.7
W261Aⁿ	wt	-7.00	8.20	-20.7	0.1	41	1	81.8	63.2	45.5	17.3	0.4
W263Aⁿ	wt	-6.16	8.26	-19.7	1.2	41	1	76.0	61.9	45.1	17.4	-0.6
S289Aⁿ	wt	-7.20	8.04	-20.8	0.0	44	1	82.7	64.4	47.3	17.0	0.1
W318Aⁿ	wt	-5.89	8.30	-19.3	1.5	37	1	76.6	62.0	45.7	17.4	-1.1
K320Aⁿ	wt	-7.03	8.46	-21.1	-0.3	45	1	81.9	63.6	46.0	16.8	0.8
E344Aⁿ	wt	-7.01	8.15	-20.7	0.2	43	1	81.9	63.0	45.9	16.8	0.3
W375Aⁿ	wt	-6.51	8.00	-19.8	1.0	48	1	77.4	61.8	44.9	17.7	-0.8
E401Aⁿ	wt	-6.49	8.15	-20.0	0.9	45	1	81.5	63.5	46.1	17.1	0.3
W261A/W263A/W318Aⁿ	wt	-3.51	7.96	-15.6	5.2	31	11	68.0	57.9	42.5	17.6	-2.2
W261A/W263A/W318Aⁿ	R5A	-1.39	7.89	-12.6	8.2	28	39	63.7	55.3	40.8	15.3	-0.8
W261A/W263A/W318Aⁿ	K40G	-0.96	7.59	-11.7	9.2	24	58	61.1	53.9	41.5	14.0	-1.6
Y434A^p	wt	-5.14	7.88	-17.7	3.1	45	1	78.1	59.8	43.1	17.2	-0.5
D435A^p	wt	-4.85	8.00	-17.5	3.3	44	1	77.5	59.6	44.6	14.1	0.9
Y437A^p	wt	-6.51	8.30	-20.2	0.6	41	1	76.8	60.5	43.3	17.5	-0.3
des (S460)^p	wt	-6.20	8.28	-19.7	1.1	44	1	81.3	63.5	46.0	17.2	0.3

^adecimal logarithm of the dissociation rate constant k_d(s^-1). Experimental value from Ref. [13].
^bdecimal logarithm of the association rate constant k_a(M^-1s^-1). Experimental value from Ref. [13].
^cstandard free energy of association as obtained from the relationship ΔG° = RT ln K_D, where K_D=k_d/k_a.
^ddifference in binding free energy for the wild type and variant complexes, calculated from the equation ΔΔG = -RT ln (K_D,wt/K_D,var).
^enumber of native-like solutions among the ensemble of 12000 solutions (i.e. derived from three independent docking runs each ranking 4000 solutions).
^frank number of the best native-like solution in the output list (i.e. 1 = highest scored ; 12000 = lowest scored).
^gZD scores of the best native-like solution in the output list
^hZD scores averaged over all the native-like complexes resulting from three independent runs; ⁱshape complementarity term; ^l electrostatic term; ^m desolvation term. See Methods.
ⁿexperimental data from [13] (Tables 2, 3, and 5).
^orecombinant hRI in which Ser460 is deleted. Nomenclature from Ref. [7] ^p experimental data from Ref. [7] (Table 4).

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