Silva Carlos H T P, Almeida Paulo, Taft Carlton A
Instituto de Física de São Carlos, Universidade de São Paulo, Caixa Postal 369, São Carlos, SP, Brazil.
J Mol Model. 2004 Feb;10(1):38-43. doi: 10.1007/s00894-003-0167-4. Epub 2003 Nov 22.
The retinoic acid receptor (RAR) and retinoid X receptor (RXR) are members of the nuclear receptor superfamily. The ligand-binding domain contains the ligand-dependent activation function. The isotypes RARalpha,beta and gamma are distinct pharmacological targets for retinoids involved in the treatment of various cancers and skin diseases. There is thus considerable interest in synthetic retinoids with isotype selectivity and reduced side effects. In this work we have focused on the retinoid acid receptor and three of its panagonists. We have carried out density functional geometry optimizations at the B3LYP/6-31G* level, computed two types of atomic charges and also electrostatic potentials. A docking program was used to investigate the interactions between the receptor and the three ligands. A theoretically more potent inhibitor, which was obtained by modifying one of the retinoic acids investigated, is proposed.
维甲酸受体（RAR）和类视黄醇X受体（RXR）是核受体超家族的成员。配体结合域包含配体依赖性激活功能。RARα、β和γ亚型是参与治疗各种癌症和皮肤病的类视黄醇的不同药理学靶点。因此，具有亚型选择性和减少副作用的合成类视黄醇备受关注。在这项工作中，我们重点研究了维甲酸受体及其三种泛激动剂。我们在B3LYP/6-31G*水平上进行了密度泛函几何优化，计算了两种类型的原子电荷以及静电势。使用对接程序研究受体与三种配体之间的相互作用。提出了一种通过修饰所研究的一种维甲酸而获得的理论上更有效的抑制剂。
