Gypsum-DL: an open-source program for preparing small-molecule libraries for structure-based virtual screening.

Area of Science:

• Computational chemistry
• Cheminformatics
• Drug discovery

Background:

• Structure-based virtual screening requires accurate 3D ligand models.
• Existing commercial software has licensing restrictions.
• Free alternatives often lack comprehensive tautomeric and isomeric form generation.

Purpose of the Study:

• Introduce Gypsum-DL, a free, open-source program for virtual library preparation.
• Address limitations of existing software in generating diverse molecular forms.
• Enhance the accuracy of computational drug discovery methods.

Main Methods:

• Gypsum-DL accepts virtual compound libraries (SMILES or SDF format).
• It enumerates ionization, tautomeric, isomeric, and ring-conformational variants.
• Generates 3D coordinates for each molecular form in SDF format.

Main Results:

• Processed 1558 molecules from NCI Diversity Set VI and 56,608 from a D3 library.
• Demonstrated improved virtual screening pose prediction using PDBBind complexes.
• Gypsum-DL successfully generated diverse molecular forms for large virtual libraries.

Conclusions:

• Gypsum-DL provides a robust, free solution for preparing 3D small-molecule models.
• The program enhances the quality and diversity of input for virtual screening.
• Gypsum-DL facilitates more accurate computational drug discovery and pose prediction.