TOPO for folded-protein simulations

An OpenMM-based package for topology-based coarse-grained simulations of folded proteins

TOPO builds a one-bead-per-residue, structure-based (Gō-like) model from a folded-protein structure for coarse-grained molecular dynamics.

TOPO (TOPOlogy-based coarse-grained model for folded prOteins) is a Python library and command-line toolkit for coarse-grained molecular dynamics of globular (folded) proteins, built on the OpenMM engine. From a single PDB/CIF structure, it automatically builds a one-bead-per-residue (Cα) structure-based (Gō-like) model where the native fold is the energy minimum — ideal for studying folding, unfolding, thermal and mechanical stability, and multidomain motions.

The model

  • One bead per residue (alpha-carbon), carrying its amino-acid mass, charge, and radius.
  • Bonded terms: rigid/harmonic Cα–Cα bonds, a bimodal backbone-angle potential (helical + extended basins), and sequence-dependent torsions.
  • Non-bonded terms: Debye–Hückel screened electrostatics plus a 12-10-6 Gō-type contact potential.
  • Native contacts (from STRIDE H-bonds + heavy-atom proximity) get attractive wells at native distances; all other pairs get soft excluded-volume repulsion.
  • Implicit solvent (no explicit water/box) and a large 15 fs time step via bond constraints.

Key features

  • Single-domain quickstart: one md.ini control file, one structure, run and analyze.
  • Multidomain proteins with per-domain and per-interface contact scaling via domain.yaml (including discontiguous domains).
  • Automatic contact nscale optimization (topo-optimize) — finds the smallest scale that keeps each domain/interface folded.
  • Temperature annealing and quenching to unfold then refold, with separate quench/production trajectories.
  • Native-contact (Q) analysis to measure how folded the protein and each domain is, frame by frame.
  • Checkpoint restart for long runs, and many copies in one GPU-filling simulation for independent trajectories.
  • Co-translational protein synthesis (topo.csp) — grow the chain residue by residue under codon-resolved kinetics, either through an analytic cylinder tunnel (topo-cylinder) or on an explicit coarse-grained ribosome (topo-csp).
  • CPU/GPU execution, command line (topo-mdrun) plus a Python API for scripting.

Relationship to COSMO

  • Companion to COSMO (adapted from its code base): COSMO targets disordered proteins, TOPO targets folded ones.
  • Both packages support co-translational protein synthesis with the same two exit-tunnel models (cylinder and coarse-grained ribosome).

Code and documentation: