2023/08/31 by Adrian Krzyzanowski, Axel Pahl, Michael Grigalunas +1 · 1 voice · 4 citations
Biochemistry, Genetics and Molecular Biology · Computer Science · Medicine · #Bioinformatics and Genomic Networks #Computational Drug Discovery Methods #Microbial Natural Products and Biosynthesis
paper · pdf · doi:10.1021/acs.jmedchem.3c00689
openalex publication_date 2023/08/31 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/26
High Resolution Image Download MS PowerPoint Slide The fraction of sp 3 -hybridized carbons ( F sp 3 ) and the fraction of stereogenic carbons ( F Cstereo ) are two widely employed scores of molecular complexity with strong links to biologically relevant features. However, they do not comprehensively express molecular topology, and they often do not match the chemical intuition of complexity. We propose the spacial score (SPS) as an empirical scoring system that builds upon the principle underlying F sp 3 and F Cstereo and expresses the spacial complexity of a compound in a uniform manner on a highly granular scale. The size-normalized SPS (nSPS) can differentiate distributions of natural products and synthetic compounds and is applicable in the analysis of biological activity data. Analysis of the ChEMBL database revealed general trends of increasing selectivity and potency with increasing nSPS. SPS can also be used advantageously in planning and analysis of synthesis programs for direct comparison of chemical transformations and intermediates in reaction sequences.