Table 7.

MM-PBSA binding free energy analysis of CDK2-ligand (1, 2a-2i, and 3) and ATP Complexes, all energy values are in kcal/mol. Values represent average binding energies from molecular dynamics simulations.

Compound	ΔVDWAALS	ΔE_EEL	ΔG_GAS	ΔE_PB	ΔENPOLAR	ΔG_SOLV	ΔG_bind	SEM
1	−37.79	−16.98	−54.77	47.58	−4.23	43.35	−11.43	± 0.34
2a	−51.77	−29.93	−81.70	66.48	−5.09	61.39	−20.30	± 0.31
2b	−51.36	−26.68	−78.04	63.17	−5.15	58.02	−20.02	± 0.32
2c	−50.95	−36.21	−87.15	61.56	−5.34	56.22	−30.94	± 0.39
2d★	−50.74	−30.91	−81.65	52.40	−5.26	47.15	−34.50	± 0.42
2e	−43.58	−16.77	−60.35	45.05	−4.58	40.47	−19.88	± 0.25
2f	−41.31	−41.49	−82.80	70.14	−4.86	65.29	−17.51	± 0.28
2 g	−49.20	−28.96	−78.17	69.66	−5.02	64.64	−13.52	± 0.38
2 h	−43.20	−11.14	−54.34	50.21	−4.47	45.73	−8.61	± 0.37
2i	−48.35	−17.28	−65.63	47.11	−4.94	42.17	−23.46	± 0.36
3	−41.55	−10.14	−51.69	43.91	−4.25	39.66	−12.03	± 0.30
ATP	−33.07	−947.61	−980.68	925.44	−4.43	921.00	−59.68	± 1.17

ΔVDWAALS: Van der Waals contribution to binding. ΔE_EEL: Electrostatic energy contribution. ΔG_GAS: Total gas-phase free energy. ΔE_PB: Polar solvation energy (Poisson-Boltzmann). ΔE_NPOLAR: Non-polar solvation energy. ΔG_SOLV: Total solvation free energy. Δ_G_bind: Total binding free energy. SEM: Standard error of the mean.

★ indicates the compound with the most favorable binding energy. More negative ΔG_bind values indicate stronger binding affinity.