Protein-Ligand Complex Generator & Drug Screening via Tiered Tensor Transform

Understand

The generation of small molecule candidate (ligand) binding poses in its target protein pocket is important for computer-aided drug discovery.

• Typical rigid-body docking methods ignore the pocket flexibility of protein, while the more accurate pose generation using molecular dynamics is hindered by slow protein dynamics.
• We develop a tiered tensor transform (3T) algorithm to rapidly generate diverse protein-ligand complex conformations for both pose and affinity estimation in drug screening, requiring neither machine learning training nor lengthy dynamics computation, while maintaining both coarse-grain-like coordinated protein dynamics and atomistic-level details of the complex pocket.
• The 3T conformation structures we generate achieve significantly higher accuracy in active ligand classification than traditional ensemble docking using hundreds of experimental protein conformations.