Department of Pharmaceutical Chemistry, Philipps-Universität Marburg, Marbacher Weg 6, Germany.
J Chem Inf Model. 2011 Oct 24;51(10):2731-45. doi: 10.1021/ci200274q. Epub 2011 Oct 4.
We introduce the new knowledge-based scoring function DSX that consists of distance-dependent pair potentials, novel torsion angle potentials, and newly defined solvent accessible surface-dependent potentials. DSX pair potentials are based on the statistical formalism of DrugScore, extended by a much more specialized set of atom types. The original DrugScore-like reference state is rather unstable with respect to modifications in the used atom types. Therefore, an important method to overcome this problem and to allow for robust results when deriving pair potentials for arbitrary sets of atom types is presented. A validation based on a carefully prepared test set is shown, enabling direct comparison to the majority of other popular scoring functions. Here, DSX features superior performance with respect to docking- and ranking power and runtime requirements. Furthermore, the beneficial combination with torsion angle-dependent and desolvation-dependent potentials is demonstrated. DSX is robust, flexible, and capable of working together with special features of popular docking engines, e.g., flexible protein residues in AutoDock or GOLD. The program is freely available to the scientific community and can be downloaded from our Web site www.agklebe.de .
我们引入了新的基于知识的评分函数 DSX，它由距离相关的对势能、新的扭转角势能和新定义的溶剂可及表面相关的势能组成。DSX 对势能基于 DrugScore 的统计形式，扩展了一套更专门的原子类型。原始的类似 DrugScore 的参考状态对于所使用的原子类型的修改相当不稳定。因此，提出了一种重要的方法来克服这个问题，并允许在为任意原子类型集导出对势能时获得稳健的结果。基于精心准备的测试集进行了验证，使其能够与大多数其他流行的评分函数进行直接比较。在这里，DSX 在对接和排序能力以及运行时需求方面表现出卓越的性能。此外，还证明了与扭转角相关和去溶剂化相关势能的有益组合。DSX 具有稳健性、灵活性，并且能够与流行的对接引擎的特殊功能一起使用，例如 AutoDock 或 GOLD 中的柔性蛋白质残基。该程序可供科学界免费使用，并可从我们的网站 www.agklebe.de 下载。
