Abstract
Abstract
We present SOP-Multi-
π
, an enhanced version of the two-bead-per-amino-acid resolution Self-Organized Polymer (SOP) model designed to investigate the conformational dynamics of Intrinsically Disordered Proteins (IDPs) and their phase behavior in biomolecular condensates. The original SOP-IDP and SOP-Multi models work well for chains in good solvents that predominantly adopt expanded conformations. However, they fail to reproduce the single-chain properties and phase-separation behavior of IDPs such as hnRNPA1 and its variants, which have a distinct pattern of aromatic residues. We therefore reparameterized the SOP-IDP force field to explicitly capture
π
–
π
and cation–
π
interactions at the coarse-grained (CG) resolution. These interactions are weak but important for biomolecular recognition and for driving and stabilizing biomolecular condensates. Dimensionless rescaling prefactors (
λ
ij
) were applied exclusively to the aromatic
π
–
π
(Phe, Tyr, Trp) and cation–
π
(Arg/Lys with Phe, Tyr, Trp) pairs. They were optimized iteratively against experimental radii of gyration of the hnRNPA1 low-complexity domain (A1-LCD) and its 16 aromatic and charge mutants. This restored a physically meaningful Tyr
>
Phe interaction hierarchy, and the Pearson correlation for
R
g
improved from
r
= 0.07 (SOP-IDP) to
r
= 0.83 (RMSD = 0.08 nm). The same parameters, without further tuning, gave
r
= 0.93 for 34 additional IDPs (24–198 residues) and reproduced Flory scaling (
ν
≈ 0.588). We back-mapped microsecond-scale CG ensembles to all-atom representations and computed SAXS and Kratky profiles for direct comparison with experiments on IDPs and on the multidomain proteins hnRNPA1, TDP-43, G3BP1, and FUS. In direct-coexistence slab simulations, the model captures the phase behavior of A1-LCD condensates and their variants, with critical temperatures that correlate strongly with experiment (
r
= 0.88) but are somewhat underestimated in absolute terms. The model is implemented in LAMMPS, and a detailed user manual is provided for setting up single-chain and multi-chain condensate simulations of full-length multidomain proteins.