CONFORMATIONAL-ANALYSIS OF FLEXIBLE LIGANDS IN MACROMOLECULAR RECEPTOR-SITES
CONFORMATIONAL-ANALYSIS OF FLEXIBLE LIGANDS IN MACROMOLECULAR RECEPTOR-SITES
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DOI：
10.1002/jcc.540130608
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发表时间：
1992-07-01
影响因子：
3
通讯作者：
KUNTZ, ID
中科院分区：
文献类型：
--
作者：
LEACH, AR;KUNTZ, ID
提出了一种探索大分子受体位点内柔性配体的取向和构象空间的计算方法。该方法使用DOCK算法的一种变体[Kuntz et al.， J. Mol. Biol]。[j], 161,288(1982)]来确定位点内配体片段的方向。然后，这些位置形成了利用系统搜索算法探索配体其余构象空间的基础。该搜索结合了一种方法，通过该方法可以根据与受体的相互作用修改配体构象。该方法应用于两个测试案例，在这两个测试案例中都获得了晶体学确定的结构。然而，也可以得到与实验观察到的有很大不同的替代模型。讨论了分子间相互作用的各种措施区分这些结构的能力。
A computational method for exploring the orientational and conformational space of a flexible ligand within a macromolecular receptor site is presented. The approach uses a variant of the DOCK algorithm [Kuntz et al., J. Mol. Biol., 161, 288 (1982)] to determine orientations of a fragment of the ligand within the site. These Positions then form the basis for exploring the conformational space of the rest of the ligand, using a systematic search algorithm. The search incorporates a method by which the ligand conformation can be modified in response to interactions with the receptor. The approach is applied to two test cases, in both of which the crystallographically determined structures are obtained. However, alternative models can also be obtained that differ significantly from those observed experimentally. The ability of a variety of measures of the intermolecular interaction to discriminate among these structures is discussed.