PlayMolecule ProteinPrepare: A Web Application for Protein Preparation for Molecular Dynamics Simulations

Area of Science:

• Computational Biology
• Structural Biology
• Biophysics

Background:

• Protein structure refinement is essential for accurate molecular simulations.
• Assigning correct titration states and optimizing hydrogen bonds are critical steps.
• Existing methods can be complex and time-consuming.

Purpose of the Study:

• To introduce ProteinPrepare, a web application for interactive protein structure preparation.
• To facilitate the assignment of titration states and optimization of hydrogen-bonding networks.
• To improve the efficiency and accessibility of protein preparation for molecular simulations.

Main Methods:

• Development of a web application with a 3D interactive interface.
• Automated suggestion of protonation states based on solvent pH.
• Manual adjustment of protonation states guided by hydrogen-bonding network visualization.
• Provision of pKa values, charge states, and visual alerts for manual review.
• Inclusion of an offline script for High-Throughput Molecular Dynamics (HTMD) integration.

Main Results:

• ProteinPrepare enables users to upload PDB files and visualize protonation states and hydrogen bonds.
• The application provides automated suggestions for protonation states, with options for manual correction.
• Visualizations and data tables aid in assessing the validity of protein preparation.
• An offline script allows for non-interactive preparation using HTMD.

Conclusions:

• ProteinPrepare offers a user-friendly, interactive tool for critical protein preparation steps in molecular simulations.
• The combination of automated suggestions and interactive visualization enhances the accuracy and efficiency of structure refinement.
• The tool supports both interactive and high-throughput preparation workflows, broadening its applicability.