A high-throughput molecular docking facility is presented for screening combinatorial libraries to identity binding ligands and ultimately pharmaceutical compounds. The facility employs a pre-coking conformational search to generate multiple solution conformations of a ligand. The molecular docking facility includes: generating a binding site image of the target molecule, the binding site image to atoms in at least one solution conformation of the multiple solution conformations of the ligand to obtain at least one ligand postion relative to the target molecule in a ligand-target molecule complex formation; and optimizing the at least one ligand position while allowing translation, orientation and rotatable bonds of the ligand to vary, and while holding the target molecule fixed. Docking results are clustered using as a metric the rms deviation between the core of two docked molecules. A library is rated as to complementarity to the target molecule according to the relative number of ligands in the top cluster.
本文介绍了一种高通量分子对接设备，用于筛选组合库以确定结合
配体并最终确定药物化合物。该设备采用预焦化构象搜索来生成
配体的多个溶液构象。分子对接设备包括：生成目标分子的结合位点图像，该结合位点图像与
配体多个溶液构象中至少一个溶液构象的原子结合，以获得
配体-目标分子复合物形成过程中
配体相对于目标分子的至少一个位置；优化至少一个
配体位置，同时允许
配体的平移、定向和可旋转键变化，并保持目标分子固定。对接结果以两个对接分子核心之间的均方根偏差为指标进行聚类。根据顶端聚类中
配体的相对数量来评定库与目标分子的互补性。
