Lin_F9

Lin_F9 enhances scoring accuracy for protein–ligand docking by using a linear empirical scoring function composed of nine empirically derived terms, including a unified metal bond term to model metal–ligand interactions.

Key Features:

• Linear empirical scoring function: Combines nine empirically derived terms in a linear functional form to score protein–ligand interactions.
• Unified metal bond term: Includes a unified metal bond term specifically tailored to describe metal–ligand interactions.
• Multistage fitting with explicit waters: Parameters were obtained via a multistage fitting protocol that used explicit water-included structures.
• Benchmark performance (CASF-2016): Demonstrated scoring power on CASF-2016 with Pearson correlation coefficients of 0.680 for original crystal poses and 0.687 for locally optimized poses versus 34 other classical scoring functions.
• Performance versus Vina and docking scenarios: Outperformed Vina in scoring and ranking across end-to-end flexible docking scenarios using single or ensemble protein receptor structures in CASF-2016 and D3R Grand Challenge (GC4) test sets.
• Implementation: Implemented in a fork of Smina.

Scientific Applications:

• Structure-based drug design: Improves scoring and ranking of protein–ligand complexes for structure-based drug design studies.
• Modeling metal-containing complexes: Models metal–ligand interactions in metalloproteins and metalloenzymes via the unified metal bond term.
• Docking benchmark and method development: Serves as a benchmarked scoring function for docking method evaluation using CASF-2016 and D3R Grand Challenge (GC4) datasets.
• Flexible and ensemble receptor docking: Applicable to end-to-end flexible docking workflows using single or ensemble protein receptor structures.

Methodology:

Parameters were fitted by a multistage fitting protocol using explicit water-included structures; performance was evaluated on CASF-2016 and D3R Grand Challenge (GC4) benchmarks using Pearson correlation coefficients; implemented in a fork of Smina.