Synthetic accessibility score as a filter for virtual chemical structures in polymer materials design

Area of Science:

• Polymer Science
• Computational Chemistry
• Materials Informatics

Background:

• Virtual screening of polymers is computationally intensive due to vast chemical space.
• Synthetic accessibility score (SAscore) aids candidate reduction but was not initially suited for polymers.
• Adapting SAscore is crucial for efficient polymer design and discovery.

Purpose of the Study:

• To adapt and validate a polymer-specific synthetic accessibility score (SAscore) for efficient virtual screening.
• To assess the impact of different molecular fragment databases on polymer SAscore calculations.
• To provide accessible resources for polymer researchers.

Main Methods:

• Adapted the Ertl and Schüffenhauer SAscore algorithm for polymeric structures, handling multiple smallest repeating units (SRUs).
• Implemented a program to decompose chemical structures into fragments and calculate frequencies.
• Utilized PubChem Compounds and Aurora Fine Chemicals databases for fragment sourcing.

Main Results:

• The polymer-adapted SAscore effectively filters polymer structures.
• SAscore calculations showed minimal fluctuations across different fragment databases in most cases.
• Notable SAscore variations occurred for structures with rare fragments.

Conclusions:

• The developed polymer-adapted SAscore is a viable tool for reducing computational demands in polymer design.
• Fragment source choice has a minor impact on SAscore, but rare fragments require careful consideration.
• Publicly accessible databases of molecular fragments and polymer SAscores are provided to aid research.