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.