Molecular fingerprints are indispensable tools in cheminformatics. However, stereochemistry is generally not considered, which is problematic for large molecules which are almost all chiral. Herein we report MAP4C, a chiral version of our previously reported fingerprint MAP4, which lists MinHashes computed from character strings containing the SMILES of all pairs of circular substructures up to a diameter of four bonds and the shortest topological distance between their central atoms. MAP4C includes the Cahn-Ingold-Prelog (CIP) annotation (R, S, r or s) whenever the chiral atom is the center of a circular substructure, a question mark for undefined stereocenters, and double bond cis–trans information if specified. MAP4C performs slightly better than the achiral MAP4, ECFP and AP fingerprints in non-stereoselective virtual screening benchmarks. Furthermore, MAP4C distinguishes between stereoisomers in chiral molecules from small molecule drugs to large natural products and peptides comprising thousands of diastereomers, with a degree of distinction smaller than between structural isomers and proportional to the number of chirality changes. Due to its excellent performance across diverse molecular classes and its ability to handle stereochemistry, MAP4C is recommended as a generally applicable chiral molecular fingerprint. The ability of our chiral fingerprint MAP4C to handle stereoisomers from small molecules to large natural products and peptides is unprecedented and opens the way for cheminformatics to include stereochemistry as an important molecular parameter across all fields of molecular design.

中文翻译：

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一种手性指纹即可找到所有这些

分子指纹是化学信息学中不可或缺的工具。然而，通常不考虑立体化学，这对于几乎都是手性的大分子来说是有问题的。在此，我们报告了 MAP4C，它是我们之前报告的指纹 MAP4 的手性版本，它列出了根据包含所有圆形子结构对的 SMILES 的字符串计算得出的 MinHashes，最大直径为四个键，以及它们的中心原子之间的最短拓扑距离。当手性原子是圆形子结构的中心时，MAP4C 包括 Cahn-Ingold-Prelog (CIP) 注释（R、S、r 或 s）、未定义立体中心的问号以及双键顺反信息（如果指定）。在非立体选择性虚拟筛选基准中，MAP4C 的表现略好于非手性 MAP4、ECFP 和 AP 指纹。此外，MAP4C可以区分手性分子中的立体异构体，从小分子药物到大型天然产物和包含数千种非对映体的肽，其区分程度小于结构异构体之间的区分程度，并且与手性变化的数量成正比。由于其在不同分子类别中的优异性能及其处理立体化学的能力，MAP4C 被推荐作为普遍适用的手性分子指纹。我们的手性指纹 MAP4C 处理从小分子到大天然产物和肽的立体异构体的能力是前所未有的，并为化学信息学将立体化学纳入分子设计所有领域的重要分子参数开辟了道路。