Evaluating SIRAH Force Field for Modeling Spontaneous and Redox-Responsive Peptide Self-Assembly

Peptide self-assembly encompasses both spontaneous organization of molecules into stable nanostructures and active assembly controlled by external stimuli. Studying spontaneous assembly is crucial for understanding inherent peptide aggregation mechanisms and designing robust materials, while active, stimuli-responsive assembly enables dynamic control over material properties for applications in drug delivery and smart biomaterials. This study evaluates the performance of the SIRAH coarse-grained force field in simulating both spontaneous and redox-responsive peptide assemblies. Using experimentally characterized sequences and comparisons with established MARTINI simulations, preliminary results reveal significant limitations in SIRAH’s predictive capabilities: it exhibits overly high aggregation tendencies and fails to distinguish aggregating from non-aggregating peptides reliably. These findings suggest that, despite its detailed interaction mapping, SIRAH requires further parameter refinement before it can be used effectively for accurate screening and design of peptide-based self-assembling systems.