What TOPO does¶

TOPO builds a single one-bead-per-residue, structure-based (Gō-like) model from a protein structure and runs Langevin dynamics on OpenMM. One force field spans the whole spectrum — globular (folded) proteins, multi-domain proteins with intrinsically disordered regions (IDRs), and fully disordered proteins (IDPs): residues you declare disordered lose their native contacts and switch to a transferable, sequence-dependent potential, so ordered and disordered parts coexist in one chain (Disordered regions and intrinsically disordered proteins).

That one model powers two complementary workflows, each with its own set of tutorials:

A. Coarse-grained simulation of folded proteins — take a fully-formed structure and study how it moves, unfolds, and comes apart.
B. Protein synthesis — grow the chain residue by residue on the ribosome and watch it fold as it is made.

Part B builds directly on the Part A model, so start with A if you are new here.

A. Coarse-grained simulation of folded and disordered proteins¶

Start from a complete structure and run structure-based MD: folding and unfolding, thermal and mechanical stability, and multidomain motions. Contact energies can be scaled per domain and per interface, so different parts of a protein can be made more or less stable. Disorder is declared in the same file: mark tails, linkers, or whole chains as disordered to simulate a multi-domain protein with IDRs — or, with every residue marked, an IDP.

Tutorials

A.1 · Single-domain quickstart — build and run your first simulation of a small single-domain protein, then read its outputs.
A.2 · Multidomain & per-domain contact scaling — control contact-energy stability within each domain and across interfaces with a domain.yaml.
A.3 · Restart & outputs — checkpoint and resume a run, and understand every file it writes.
A.4 · Many independent copies — replicate one protein into many non-interacting copies in a single job.
A.5 · Optimizing the contact scale (nscale) — automatically calibrate the per-domain and per-interface nscale so every unit stays folded.
A.6 · Anneal & quench — drive temperature ramps to melt, quench, and observe (un)folding.
A.7 · Disordered / IDR regions — mark part of a chain intrinsically disordered with a disordered: section; the folded core keeps its shape while the tails and loops stay flexible.

Reference

B. Protein synthesis¶

Grow the nascent chain N→C, one residue at a time, so the protein can fold co-translationally as it emerges from the exit tunnel. Both tutorials layer codon-resolved kinetics on the Part A model but differ in how the ribosome exit tunnel is represented — and so in which runner they use: Tutorial B.1 uses topo-cylinder (an analytic tunnel), Tutorial B.2 uses topo-csp (an explicit coarse-grained ribosome).

Tutorials

B.1 · Synthesis through an analytic tunnel — the exit tunnel is a cylindrical bore through a wall (no explicit ribosome beads); fast, never jams, and the chain folds co-translationally on egress.
B.2 · Synthesis on a coarse-grained ribosome — the ribosome-based counterpart: grow the chain through TOPO’s own truncated CG ribosome, then eject the completed protein (worked on 4c5c and P0CX28).

Reference