Investigations on Binding Pattern of Kinase Inhibitors with PPARγ: Molecular Docking, Molecular Dynamic Simulations, and Free Energy Calculation Studies

Table 1

Glide docking scores (kcal mol⁻¹), docking energies, and calculated hydrogen bond and hydrophobic interactions of TKIs and reference compound rosiglitazone bound to human PPAR gamma binding site.

Compounds	Glide XP -Score	Glide energy	Hydrogen bond (up to 3.6 Å)	Hydrophobic interactions
Ibrutinib	−10.50	−59.65	Tyr-327	His-323, Cys-256, Ser-342, Met-348, Ile-341, Leu-333, Leu-330, Arg-288, Ile-326, Tyr-473, Ser-289, His-449, Gln-289
Sorafenib	−10.49	−53.53	Ser-289, His-323, Tyr-473	Gln-286, Phe-282, Cys-285, His-449, Arg-288, Gln-343, Ser-342, Leu-333, Ile-326, Leu-330
Sunitinib	−7.75	−46.71	Glu-295	Ile-296, Phe-226, Ala-292, Met-329, Leu-228, Arg-288, Leu-333, Ile-341, Met-348, Ile-281, Leu-353, Cys-285, Leu-330
Erlotinib	−9.54	−52.56	Arg-288, Glu-343	Leu-333, Ile-341, Ser-342, Ala-292, Phe-226, Glu-295, His-323, Tyr-473, Ser-289, Tyr-327, His-449, Cys-285, Leu-330
Gefitinib	−9.10	−52.45	Leu-340, Glu-343	Ser-342, Ile-341, Val-339, Cys-285, Leu-330, Met-364, Ser-289, Ile-326, Phe-226, Met-329, Glu-295, Ala-292, Leu-333, Arg-288, Leu-228
Dabrafenib	−8.59	−50.27	Ser-342	Ser-289, His-449, Ile-326, Leu-330, Tyr-327, Met-364, Cys-285, Gly-284, Ile-341, Leu-340, Arg-288, Leu-228, Leu-333, Glu-343
Rosiglitazone	−11.28	−60.57	Gln-286, Ser-289, His-323, Tyr-473	Ile-281, Phe-282, Gly-284, Cys-285, Tyr-327, Leu-330, Ile-341, Met-348, Met-384, Leu-453, His-449