Assessment of the free binding energy of 1,25-dihydroxyvitamin D3 and its analogs with the human VDR receptor model.
1,25-dihydroxyvitamin D(3) has quite significant anticancer properties, but its strong calcemic effect in principle excludes it as a potential anticancer drug. Currently, a lot of effort is being devoted to develop potent anticancer analogs of 1,25-dihydroxyvitamin D(3) that would not induce hypercalcemia during therapy. In this work, the free binding energy of the VDR receptor with 1,25-dihydroxyvitamin D(3) and its three potent analogs (EB 1089, KH 1060 and RO 25-9022) is calculated and compared with each other. With this approach, we could estimate the relative binding affinity of the most potent analog, RO 25-9022, and also revealed a quite distinct mechanism of its interaction with VDR.
Laboratory of Theory of Biopolymers, Faculty of Chemistry, University of Warsaw, Warsaw, Poland.
Karol
K
Kamel
Andrzej
A
Kolinski
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D002117:Calcitriol / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000737:chemistry; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004734:Energy Metabolism; D006801:Humans; D006934:Hypercalcemia / Q000139:chemically induced / Q000150:complications; D008024:Ligands; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy; D011485:Protein Binding; D011487:Protein Conformation; D018167:Receptors, Calcitriol / Q000737:chemistry* / Q000378:metabolism
D000970:Antineoplastic Agents; D008024:Ligands; D018167:Receptors, Calcitriol; C579457:VDR protein, human; C074279:KH 1060; D002117:Calcitriol