Aggregation of Intrinsically Fluorescent Proteins: Combining Coarse-Grained Molecular Dynamics with Alphafold Predictions

Aggregation is a pervasive phenomenon affecting both
disordered
and folded proteins, modulated by the balance between hydrophobic
attraction and electrostatics, and generally explored by means of
molecular dynamics simulations, often performed with low-resolution
models. On the other hand, the AI based structure prediction AlphaFold
software, extremely accurate for single chains, has been recently
provided with the capability of predicting the structure of protein
complexes. In this work, we compare coarse-grained molecular dynamics
simulations to assess the relative performance of different force
fields and those of AlphaFold3 (AF3) in predicting the aggregation
of four variants of intrinsically fluorescent proteins. Our results
are useful for guiding the choice or design of new potentials for
systems containing both disordered and folded proteins and outline
a possible scheme to integrate AlphaFold with molecular dynamics simulations.