DOCK 6: Impact of new features and current docking performance.

Area of Science:

• Computational chemistry
• Drug discovery
• Molecular modeling

Background:

• Structure-based drug design (SBDD) is crucial for identifying novel therapeutics.
• The DOCK program is a widely used SBDD software.
• Continuous development is needed to improve the accuracy and efficiency of SBDD tools.

Purpose of the Study:

• To present algorithmic and methodological advancements in the DOCK 6.7 program.
• To enhance the accuracy of molecular docking and pose prediction.
• To provide an updated, robust tool for structure-based drug design.

Main Methods:

• Updated internal energy function and anchor selection control.
• Enhanced minimization options and a footprint similarity scoring function.
• Symmetry-corrected root-mean-square deviation algorithm and database filtering tools.

Main Results:

• Pose reproduction success increased from 51.4% (DOCK 4.0.2) to 73.3% (DOCK 6.7).
• Sampling failures decreased from 24.1% to 9.1%, and scoring failures decreased from 24.4% to 17.5%.
• Cross-docking and enrichment studies validated performance across diverse protein targets.

Conclusions:

• DOCK 6.7 demonstrates significant improvements in pose reproduction and overall docking performance.
• The enhanced DOCK 6.7 is a valuable tool for structure-based drug design.
• Further improvements are noted for systems involving metal ions.