Table 3.

Energetic insights: MM/PBSA calculations of menin-ligand complexes. The energy values are presented in kJ/mol as “Energy value ± Standard deviation”.

Compound	MD Run	vdW	Electrostatic	Polar Solvation	SASA	Binding Energy
MI-2-2	1	−131.5 ± 1.2	−16.2 ± 1.3	82.4 ± 2	−16.8 ± 0.1	−82.1 ± 2
	2	−123.5 ± 1.7	−20.7 ± 1.7	103.3 ± 3.9	−15.8 ± 0.2	−56.8 ± 2.9
	3	−157 ± 1.3	−2.9 ± 0.6	62.2 ± 1.3	−18.5 ± 0.1	−116.2 ± 1.5
	Avg	−137.3 ± 14.3	−13.3 ± 7.6	82.6 ± 16.7	−17 ± 1.1	−85 ± 24.3
36294	1	−108.3 ± 1.5	−53.6 ± 2.5	129.1 ± 2.7	−16.3 ± 0.1	−49.3 ± 1.7
	2*	−36.5 ± 3.9 *	−19.4 ± 2.8 *	50.5 ± 7.5 *	−6.1 ± 0.6 *	−11.9 ± 5.9*
	3	−126 ± 1.6	−61 ± 2.3	143.3 ± 3.4	−17.7 ± 0.1	−61.4 ± 2.1
	Avg	−117.2 ± 8.9	−57.3 ± 3.7	136.2 ± 7.1	−17 ± 0.7	−55.4 ± 6.1
71777742	1	−169.6 ± 1.8	−12.9 ± 0.8	54.4 ± 1.6	−20 ± 0.2	−148.1 ± 1.7
	2*	−75.6 ± 4.6 *	−5.5 ± 0.8 *	46.1 ± 5.3 *	−9.8 ± 0.6 *	−45 ± 6.8 *
	3	−168.9 ± 2.7	−20.6 ± 1	77.7 ± 2.1	−19.1 ± 0.2	−130.7 ± 2.1
	Avg	−169.3 ± 0.4	−16.8 ± 3.9	66.1 ± 11.7	−19.55 ± 0.5	−139.4 ± 8.7
ZINC000103526876	1	−131.4 ± 1.5	−37.4 ± 1.8	106.3 ± 3.6	−18.1 ± 0.2	−80.8 ± 2.7
	2	−173.7 ± 2.5	−34.1 ± 2	110.1 ± 3.3	−22.4 ± 0.2	−120.1 ± 2.5
	3	−149.3 ± 1.3	−25 ± 1.6	99.4 ± 2.2	−18.8 ± 0.1	−93.5 ± 1.8
	Avg	−151.5 ± 17.3	−32.2 ± 5.3	105.3 ± 4.4	−19.7 ± 1.9	−98.1 ± 16.4
ZINC000095913861	1	−172.8 ± 1.1	−53.3 ± 1.3	109.3 ± 2	−21.2 ± 0.1	−138 ± 1.7
	2	−163.4 ± 2.6	−27.6 ± 2.2	95.4 ± 4.1	−19.7 ± 0.3	−115.5 ± 2.3
	3	−170.3 ± 1.4	−37.8 ± 1.1	89 ± 1.3	−20.9 ± 0.1	−139.8 ± 1.7
	Avg	−168.8 ± 4	−39.6 ± 10.6	97.9 ± 8.5	−20.6 ± 0.6	−131.1 ± 11
ZINC000095912705	1	−149.9 ± 1.2	−21.1 ± 1	90.8 ± 1.8	−19.1 ± 0.1	−99.3 ± 1.5
	2	−134 ± 1.2	−22.5 ± 1.1	77.8 ± 1.7	−17.8 ± 0.1	−96.5 ± 1.5
	3	−151 ± 1.4	−18.4±1	91.4 ± 2	−19.3 ± 0.1	−97.3 ± 1.6
	Avg	−145 ± 7.8	−20.7 ± 1.7	86.7 ± 6.3	−18.7 ± 0.7	−97.7 ± 1.2
ZINC000085530497	1	−171 ± 1	−2 ± 1	80 ± 1.9	−20.3 ± 0.1	−113.3 ± 1.5
	2	−177.1 ± 1.9	−28.4 ± 1.8	103.1 ± 2.4	−20.1 ± 0.1	−122.4 ± 2.2
	3	−140.7 ± 1.3	−46.3 ± 1.2	102.3± 2.4	−17.5 ± 0.1	−102.3 ± 2
	Avg	−162.9 ± 15.9	−25.6 ± 18.2	95.1 ± 10.7	−19.3 ± 1.2	−112.7 ± 8.2
ZINC000095912718	1	−163.1 ± 1.8	−19 ± 1.3	131.4 ± 2.3	−21.4 ± 0.2	−72.1 ± 1.7
	2	−146.1 ± 1.6	−51.1 ± 1.1	72.5 ± 1.4	−18.5 ± 0.2	−143.2 ± 2.1
	3	−147.2 ± 1.1	−59.9 ± 1.3	122.6 ± 1.8	−18.9 ± 0.1	−103.4 ± 1.8
	Avg	−152.1 ± 7.7	−43.4 ± 17.6	108.8 ± 25.9	−19.6 ± 1.3	−106.3 ± 29.1
ZINC000070451048	1	−123.1 ± 1.8	−123 ± 1.7	68.3 ± 2.6	−16.3 ± 0.2	−85.4 ± 1.9
	2*	−95.4 ± 4.8 *	−28.4 ± 2.2 *	85.4 ± 5.5 *	−13.3 ± 0.6*	−51.6 ± 4.4*
	3	−165.9 ± 2.2	−18.5 ± 1.7	110.7 ± 3.4	−19.8 ± 0.2	−93.5 ± 1.6
	Avg	−144.5 ± 21.4	−70.8 ± 52.3	89.5 ± 21.2	−18.1 ± 1.8	−89.5 ± 4.1
ZINC000085530488	1	−154.9 ± 1	−34.2 ± 1.7	106.8 ± 2.3	−19.4 ± 0.1	−101.6 ± 1.8
	2	−173.9 ± 1.3	−82.1 ± 1.2	170.4 ± 1.4	−19.8 ± 0.1	−105.3 ± 1.5
	3	−147.8 ± 1.4	−29.1 ± 1.8	120.9 ± 2.8	−18 ± 0.1	−74 ± 2.3
	Avg	−158.9 ± 11	−48.4 ± 23.9	132.7 ± 27.3	−19.1 ± 0.8	−93.6 ± 14
ZINC000095912706	1	−152.8 ± 1.2	−40.6 ± 1.2	115.3 ± 2	−19.1 ± 0.1	−97.3 ± 1.5
	2	−163.8 ± 1.4	−31.9 ± 1.3	127.3 ± 2.3	−20.5 ± 0.1	−88.9 ± 1.9
	3	−165 ± 1.5	−30.4 ± 1.5	137.2 ± 3.8	−21 ± 0.2	−79 ± 2.1
	Avg	−160.5 ± 5.5	−34.3 ± 4.5	126.6 ± 9	−20.2 ± 0.8	−88.4 ± 7.4
ZINC000103580868	1	−172.4 ± 1.9	−8.6 ± 0.7	94.3 ± 3.4	−21.6 ± 0.2	−108.3 ± 3.2
	2	−177.9 ± 1.6	−1.8 ± 0.4	56.3 ± 1.8	−21.1 ± 0.2	−144.6 ± 2
	3	−153.6 ± 2.2	−2.2 ± 0.6	39.6 ± 2.3	−19.7 ± 0.2	−135.9 ± 2.8
	Avg	−168 ± 10.4	−4.2 ± 3.1	63.4 ± 22.9	−20.8 ± 0.8	−129.6 ± 15.5
ZINC000103584057	1	−128.6 ± 0.9	−1.8 ± 0.9	22.3 ± 2	−15.2 ± 0.1	−123.3 ± 1.7
	2	−165.5 ± 1.5	−4.3 ± 0.9	70.6 ± 1.6	−18.2 ± 0.1	−117.4 ± 1.9
	3	−175.6 ± 1.9	−9.8 ± 1.2	85.8 ± 1.7	−19.4 ± 0.1	−119 ± 1.7
	Avg	−156.6 ± 20.2	−5.3 ± 3.3	59.6 ± 27.1	−17.6 ± 1.8	−119.9 ± 2.5

^*denotes values excluded from the average calculation due to an unstable MD run (or ligand dissociation).