Torsion Library Reloaded: A New Version of Expert-Derived SMARTS Rules for Assessing Conformations of Small Molecules

The
Torsion Library contains hundreds of rules for small molecule
conformations which have been derived from the Cambridge Structural
Database (CSD) and are curated by molecular design experts. The torsion
rules are encoded as SMARTS patterns and categorize rotatable bonds
via a traffic light coloring scheme. We have systematically revised
all torsion rules to better identify highly strained conformations
and minimize the number of false alerts for CSD small molecule X-ray
structures. For this new release, we added or substantially modified
78 torsion patterns and reviewed all angles and tolerance intervals.
The overall number of red alerts for a filtered CSD data set with
130 000 structures was reduced by a factor of 4 compared to
the predecessor. This is of clear advantage in 3D virtual screening
where hits should only be removed by a conformational filter if they
are in energetically inaccessible conformations.

扭转规则库（Torsion Library）收录了数百条针对小分子构象的规则，这些规则源自剑桥结构数据库（Cambridge Structural Database, CSD），并由分子设计专家审定整理。该扭转规则以SMARTS模式编码，通过交通灯配色方案对可旋转键进行分类。我们已对所有扭转规则开展系统性修订，以更好地识别高张力构象，并最大限度减少针对剑桥结构数据库中小分子X射线结构的误报数量。在本次新版本发布中，我们新增或大幅修改了78条扭转模式，并复核了所有角度与容差区间。相较于前代版本，针对包含13万个结构的过滤后剑桥结构数据库数据集，红色警报总数量降低至原先的四分之一。这在三维虚拟筛选中具备显著优势：在此类筛选场景中，仅当命中化合物处于能量不可达的构象时，才应通过构象过滤器将其剔除。