The SIRAH 2.0 Force Field: Altius, Fortius, Citius

Area of Science:

• Computational Biology
• Molecular Dynamics
• Protein Structure

Background:

• Coarse-grained (CG) force fields are essential for large-scale molecular simulations.
• The SIRAH force field has been a valuable tool for protein modeling.
• Enhancements are needed to improve accuracy and broaden applicability.

Purpose of the Study:

• To introduce the upgraded SIRAH 2.0 force field for protein simulations.
• To enhance the structural description and flexibility of proteins.
• To expand the usability and performance of CG simulations.

Main Methods:

• Developed SIRAH 2.0 by modifying bonded and non-bonded interactions.
• Ported the SIRAH 2.0 force field to the AMBER simulation package.
• Applied SIRAH 2.0 to simulate calmodulin (CaM) in holo and apo forms.

Main Results:

• SIRAH 2.0 accurately describes protein structure and flexibility.
• Simulations of CaM showed stable ion coordination and near-atomistic precision for the holo form.
• CaM's EF-hands exhibited large movements upon peptide removal, and peptide-induced binding was observed.

Conclusions:

• SIRAH 2.0 effectively handles complex scenarios like metal ion coordination and protein-peptide recognition.
• The force field demonstrates capacity for unbiased conformational sampling.
• SIRAH 2.0 offers improved accuracy and flexibility for protein simulations.