Mason J S, Cheney D L
Department of Macromolecular Structure, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543, USA.
Pac Symp Biocomput. 2000:576-87. doi: 10.1142/9789814447331_0055.
The use of multiple potential 4-point three-dimensional (3-D) pharmacophores for the design of combinatorial libraries and for virtual screening is discussed. These 3-D pharmacophoric fingerprints can be calculated from both ligands and complementary to a protein site, with a common frame of reference, and can be very rapidly searched to identify common and different 4-point pharmacophoric shapes in compounds and protein sites. A new extension to the method for structure-based design is reported that uses the shape of the target site as an additional constraint. This enables the docking process, for example in library design and virtual screening, to be quantified in terms of how many, and which, pharmacophoric hypotheses can be matched by a compound or a library of compounds.
讨论了使用多个潜在的四点三维（3-D）药效团来设计组合文库和进行虚拟筛选。这些3-D药效团指纹可以从配体计算得出，并与蛋白质位点互补，具有共同的参考框架，并且可以非常快速地进行搜索，以识别化合物和蛋白质位点中常见和不同的四点药效团形状。报道了一种基于结构设计方法的新扩展，该方法将靶位点的形状用作额外的约束条件。这使得对接过程，例如在文库设计和虚拟筛选中，能够根据化合物或化合物文库可以匹配多少以及哪些药效团假设进行量化。
