Table 3.

Data on predicted binding free energies (in kcal·mol⁻¹) of compounds 1–9 with HAV 3C protease using ParDOCK, AutoDock 69, SwissDock 70, MMBAPPL, MMGBSA, and MMPBSA along with the experimentally obtained K _i values. The MMBAPPL, MMGBSA, and MMPBSA scores are obtained from 100 ns molecular dynamics simulations run

Compoundsa	Dock score (ParDOCK)	Dock score (AutoDock)	Dock score (SwissDock)	MMPBSA ± SE of mean	MMGBSA ± SE of mean	MMBAPPL ± SE of mean	Experimental K i values (μm)
Compound 1	−16.25	−7.4	−9.10	−38.60 ± 0.70	−52.20 ± 0.53	−8.96 ± 0.14	3
Compound 2	−11.05	−6.5	−9.15	−13.25 ± 0.16	−41.80 ± 0.47	−6.97 ± 0.20	8.6
Compound 3	−10.58	−9.0	−8.45	−15.78 ± 0.23	−42.56 ± 0.42	−8.56 ± 0.36	2.5
Compound 4	−10.32	−8.2	−8.83	−29.96 ± 0.58	−50.22 ± 0.12	−8.61 ± 0.11	1.4
Compound 6	−11.49	−7.0	−8.98	−18.95 ± 0.14	−57.20 ± 0.35	−9.01 ± 0.18	3.3
Compound 7	−11.25	−7.7	−8.68	−21.66 ± 0.19	−55.18 ± 0.33	−8.92 ± 0.13	1.2
Compound 8	−12.52	−7.5	−7.75	−20.23 ± 0.43	−53.87 ± 0.57	−8.19 ± 0.14	2.1
Compound 9	−14.78	−6.5	−6.96	−21.32 ± 0.11	−52.58 ± 0.25	−8.56 ± 0.14	1.6
Compound 5	−10.93	−7.3	−8.33	−27.47 ± 0.73	−46.78 ± 0.54	−6.30 ± 0.33	117.8

All the three docking software show correlation of < 0.5 w.r.t K _i values; however, the average protein–ligand score for the most stable part of complexes during their 100 ns simulation using binding free energy scoring algorithm of MMBAPPL showed a strong correlation of 0.82 w.r.t K _i values. BAPPL is the scoring algorithm utilized in ParDOCK for calculating binding free energy of the protein–ligand complex, which when calculated over all the snapshots of protein–ligand complexes during the molecular dynamics simulations is known as MMBAPPL. The score calculates energies obtained for each snapshot during the simulations and provides an average binding free energy of the complex. The success of the methodology relies on the screening (with −10 kcal·mol⁻¹ of binding free energy as threshold) as well as the overall binding affinity calculated over a period of stable molecular dynamics simulations using MMBAPPL.

^aFor calculating the correlations, the compound 5 data were not considered due to its drift from the catalytic site of protease.

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