MOSAICS Studio: all-atom natural-move Monte Carlo on modern additive force fields in the browser

Le résumé fourni par la source

Natural-move Monte Carlo displaces a structurally meaningful group of atoms as a unit and repairs the covalent geometry with a stochastic chain closure. It has mostly been run on reduced representations under knowledge-based potentials, which return a ranking and not a quantity. We report that MOSAICS, the natural-move engine, now evaluates modern additive force fields at all-atom resolution, and that MOSAICS Studio puts that engine inside a web browser. The force fields are ff14SB and ff19SB for protein, the latter with its per-residue (phi, psi) correction maps; parmbsc0, parmbsc1, OL15/OL3, OL21/OL3 and OL24/OL3 for nucleic acid; and CHARMM36 for nucleic acid, with its Urey-Bradley terms and harmonic impropers. Single-point energies were compared with sander 24.0, OpenMM 8.5.2 and GROMACS 2025.4 on eleven systems of 56 to 6,139 atoms, from free-ended 4-mers and capped peptides to a peptide-MHC class I complex and a protein-RNA complex, in 26 system-and-force-field combinations. Nineteen of the 26 agree with every available reference to within 0.001 kcal/mol; the median largest gap is 0.00037 kcal/mol; the worst, 0.043 kcal/mol on BPTI under ff19SB, is one improper whose atom order differs between the AMBER topology and the MOSAICS residue template. Term by term, on an 818-atom DNA:RNA heteroduplex and a capped peptide, the largest difference from OpenMM on any term is 1.8e-4 and 9.6e-6 kcal/mol, both on the angle term and both arising in the reference topology. The charge-to-energy constant was measured, not assumed: it differs between these programs by enough to move the heteroduplex by 0.064 kcal/mol. Analytic forces track a central difference of the same energy at second order in 61 term-and-system sweeps, and one Monte Carlo step at 818 atoms costs 3.46 ms on one core. MOSAICS Studio runs the engine, compiled to WebAssembly, and its own preparation and analysis pipeline inside the visitor's browser tab, so nothing is installed and nothing is uploaded; a documented minimisation reproduces between the native and WebAssembly engines to the same 2,040 iterations, the same first and last energies, and 0.0045 A between final structures, and every run carries a record naming the engine, the parameter files and the inputs by digest. The chemistry and geometries tested bound every claim: one conformation per system, in vacuum, with no cutoff. This deposit holds the manuscript sources, the Supporting Information, the scripts that generate the tables and figures, and the evidence trees behind every number in the paper. The compiled manuscript is main.pdf and the Supporting Information is si.pdf. MOSAICS Studio runs at https://www.cs.ox.ac.uk/mosaics/mosaics-studio/.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.