Fragment-based docking: development of the CHARMMing Web user interface as a platform for computer-aided drug design

Area of Science:

• Computational chemistry
• Molecular modeling
• Bioinformatics

Background:

• Web-based interfaces are crucial for accessing scientific software.
• CHARMMing (CHARMM interface and graphics) provides access to the CHARMM molecular package.
• Existing CHARMMing features include molecular structure analysis, dynamics, and multiscale modeling.

Purpose of the Study:

• To extend CHARMMing's capabilities with a fragment-based docking protocol.
• To enable molecular docking and virtual screening via a web server or generated job scripts.
• To evaluate the performance of the new docking protocol.

Main Methods:

• Implementation of a fragment-based docking protocol within CHARMMing.
• Utilizing the CHARMMing web server for direct calculations.
• Generating self-contained job scripts for external computation.
• Performing re-docking evaluations and comparing with commercial software.

Main Results:

• The new protocol allows molecular docking and virtual screening.
• Users can perform calculations via the CHARMMing web server or using generated scripts.
• The CHARMMing docking implementation shows performance comparable to commercial software.
• Validation of the new CHARMM generalized force field for docking and virtual screening.

Conclusions:

• CHARMMing's extended capabilities now include a robust fragment-based docking protocol.
• The protocol is suitable for both direct web server use and external computation.
• The performance is competitive with established commercial docking software.
• The CHARMM generalized force field is validated for docking and virtual screening applications.