CABS-flex 3.0: an online tool for simulating protein structural flexibility and peptide modeling.

Area of Science:

• Computational Biology
• Structural Biology
• Biophysics

Background:

• Simulating protein flexibility is computationally intensive for large proteins.
• Classical methods often struggle with the speed and scale required for dynamic protein analysis.
• Existing tools may lack comprehensive features for diverse modeling needs.

Purpose of the Study:

• To introduce CABS-flex 3.0, a major upgrade to the CABS-flex web server for fast protein structural flexibility simulations.
• To provide enhanced capabilities for de novo peptide structure prediction and analysis of conformational flexibility.
• To improve the user experience with intuitive controls, better model generation, and advanced analysis tools.

Main Methods:

• Utilizing a hybrid coarse-grained and all-atom simulation approach for efficient protein flexibility studies.
• Implementing new flexibility modes for simplified control of distance restraints and dynamic regions.
• Incorporating de novo peptide structure prediction for linear and cyclic peptides.
• Integrating AlphaFold pLDDT-derived restraints as optional simulation input.
• Offering PDB/mmCIF structure or sequence as input, with advanced options for experimental/computational restraints.

Main Results:

• CABS-flex 3.0 offers significantly improved speed and accuracy in simulating protein structural flexibility.
• The new peptide modeling feature enables prediction of both linear and cyclic peptide structures with conformational flexibility.
• Enhanced all-atom reconstruction leads to higher-quality protein models.
• New analysis and visualization tools provide deeper insights into protein dynamics.
• Optional integration of AlphaFold restraints guides simulations more effectively.

Conclusions:

• CABS-flex 3.0 represents a substantial advancement in computational tools for studying protein and peptide structural flexibility.
• The enhanced features and improved usability make it a valuable resource for researchers in structural biology and computational chemistry.
• The web server provides a free and accessible platform for diverse modeling and analysis tasks.