Employing “FAST Water” to Accelerate Self-Assembly

Abstract

Abstract Molecular dynamics (MD) simulations are a powerful tool for elucidating the molecular mechanisms of supramolecular self-assembly, but the long time scales of aggregation often make all-atom simulations computationally challenging. Here, we evaluate the recently developed TIP3P-FAST water model as a simple strategy to accelerate self-assembly simulations in an aqueous solution. TIP3P-FAST employs mass repartitioning and rescaling within a water molecule, increasing the molecular mobility without altering the underlying potential energy surface. We investigate three representative self-assembling systems with distinct aggregation mechanisms and resulting morphologies: l-phenylalanine tripeptide (FFF), methyl-substituted ureido-pyrimidinone (UPy), and sodium dodecyl sulfate (SDS). Simulations of isolated solutes reveal an around 2.5-fold increase in diffusion coefficients in TIP3P-FAST water compared to conventional TIP3P water, while solvent-accessible surface areas, radial distribution functions, hydrogen-bond numbers, and interaction energies remain unchanged. Self-assembly simulations initiated from dispersed monomers show markedly accelerated aggregation kinetics in FAST water, as evidenced by a faster decrease in solvent-accessible surface area and the number of clusters. For UPy, enhanced dynamics facilitate more efficient structural reorganization, yielding assemblies with characteristics comparable to or even more ordered than those obtained in TIP3P water at the same interval. These results demonstrate that TIP3P-FAST substantially reduces the computational cost of atomistic self-assembly simulations while preserving the equilibrium structural and thermodynamic properties, providing a practical route for studying complex supramolecular systems.