Comparative Assessment of Scoring Functions: The CASF-2016 Update

Area of Science:

• Computational chemistry
• Structural biology
• Drug discovery

Background:

• Scoring functions are crucial for evaluating protein-ligand interactions in structure-based drug design.
• Existing scoring functions require objective benchmarks to assess their performance and limitations.

Purpose of the Study:

• To introduce CASF-2016, an updated benchmark for evaluating the performance of scoring functions in drug design.
• To provide a standardized and objective method for comparing different scoring functions.

Main Methods:

• The CASF-2016 benchmark decouples the scoring process from docking for precise scoring function evaluation.
• A new test set of 285 protein-ligand complexes with high-quality crystal structures and binding constants was compiled.
• 25 scoring functions were tested using four metrics: scoring, ranking, docking, and screening power.

Main Results:

• Current scoring functions demonstrate stronger performance in docking power compared to scoring, ranking, and screening power.
• A correlation was observed between scoring power and ranking power, and similarly between docking power and screening power.
• The benchmark provides valuable insights for selecting appropriate scoring functions in drug design.

Conclusions:

• CASF-2016 offers a robust evaluation of scoring functions, aiding researchers in making informed choices.
• The open-access nature of CASF-2016 encourages broader testing and development of scoring functions.
• The benchmark results highlight areas for improvement in current scoring function methodologies.