Automated builder and database of protein/membrane complexes for molecular dynamics simulations

Area of Science:

• Biophysics
• Computational Biology
• Structural Biology

Background:

• Molecular dynamics (MD) simulations offer atomic-level insights into membrane protein function.
• Constructing realistic protein/membrane complexes for MD is complex and requires specialized expertise.
• Existing methods for membrane system preparation are often time-consuming and challenging for non-experts.

Purpose of the Study:

• To present Membrane Builder, a web-based tool within CHARMM-GUI, for automated construction of membrane protein simulation systems.
• To simplify and accelerate the process of building complex, realistic membrane protein/lipid bilayer models.
• To provide an accessible platform for both novice and expert users to generate membrane simulation systems.

Main Methods:

• Utilizes a graphical user interface within a web browser for system building.
• Employs a generalized and automated workflow including system size determination, lipid bilayer generation, pore and bulk water inclusion, and ion placement.
• Offers default parameters, extensively tested, to guide users through the process.

Main Results:

• Successfully generated realistic membrane systems for 12 transmembrane and 3 interfacial proteins.
• Demonstrated rapid system generation, ranging from 5 minutes to 2 hours depending on system size.
• Provided freely available, fully equilibrated simulation systems with various lipid types (DMPC, DPPC, POPC) and shapes (rectangular, hexagonal).

Conclusions:

• Membrane Builder significantly lowers the barrier to entry for performing membrane protein simulations.
• The automated, web-based approach streamlines the creation of complex biological membrane models.
• Facilitates easier and more intuitive simulation of biologically crucial membrane systems.