Roe D C, Kuntz I D
Department of Pharmaceutical Chemistry, University of California, San Francisco 94143-0446, USA.
J Comput Aided Mol Des. 1995 Jun;9(3):269-82. doi: 10.1007/BF00124457.
Significant improvements have been made to the de novo drug design program BUILDER. The BUILDER strategy is to find molecule templates that bind tightly to 'hot spots' in the target receptor, and then generate bridges to join these templates. In this paper, the bridging algorithm has been further developed to improve the chemical sense and diversity of the bridges, as well as the robustness of the technique. The improved algorithm is then applied to rebuild known bridges in methotrexate and HIV protease. Finally, the entire BUILDER approach is tested by rebuilding methotrexate de novo.
从头药物设计程序BUILDER已经有了显著改进。BUILDER的策略是找到能紧密结合到目标受体“热点”的分子模板，然后生成连接这些模板的桥连结构。在本文中，桥连算法得到了进一步发展，以提高桥连结构的化学合理性和多样性，以及该技术的稳健性。然后将改进后的算法应用于重建甲氨蝶呤和HIV蛋白酶中的已知桥连结构。最后，通过从头重建甲氨蝶呤对整个BUILDER方法进行了测试。
