Molecular dynamics
Steered molecular dynamics
Review structures and compatible trajectories from steered simulations while keeping force, work, pathway, and protocol claims tied to the external run.
Inputs
2 required
Methods
1 connected
- 01MD Trajectory Analysis · Steered MD Review
Upload a compatible topology and trajectory from an external steered run for RMSD, RMSF, distance, and compactness review.
Use this templateWhat is steered molecular dynamics?
Steered molecular dynamics is a simulation method that applies a time-dependent restraint or force along a selected coordinate to drive a molecular system through a transition. Common uses include ligand unbinding, domain separation, protein unfolding, and pathway generation. The observed response depends on pulling geometry, spring constant, velocity, environment, and starting state, so one forced trajectory is not an equilibrium mechanism or binding free energy.
Design the pulling coordinate around a concrete physical hypothesis. Define pulled and reference groups, periodic-boundary treatment, restraint direction, loading rate, equilibration, and independent starting conformations before simulation. Faster pulling improves throughput but usually increases nonequilibrium dissipation and can favor artificial pathways.
ProteinIQ does not currently execute the pulling protocol or calculate force–extension and work profiles. The connected workflow reviews a compatible trajectory with MDAnalysis-based structural metrics. Preserve the external engine inputs, pull output, force and work series, and replicate-level results alongside that review.
When to use steered molecular dynamics
- Best fit. Forced unbinding, unfolding, separation, and pathway hypotheses
- Required evidence. Externally generated topology and trajectory plus pull-coordinate, force, work, and replicate records
Benefits of steered molecular dynamics
- Drives otherwise slow transitions. Drives otherwise slow transitions for projects focused on forced unbinding, unfolding, separation, and pathway hypotheses.
- Tests explicit mechanical hypotheses. Tests explicit mechanical hypotheses for projects focused on forced unbinding, unfolding, separation, and pathway hypotheses.
- Generates candidate pathways. Generates candidate pathways for projects focused on forced unbinding, unfolding, separation, and pathway hypotheses.
Primary limitations
- Strongly protocol dependent. Strongly protocol dependent. Address this with externally generated topology and trajectory plus pull-coordinate, force, work, and replicate records.
- Nonequilibrium work needs careful treatment. Nonequilibrium work needs careful treatment. Address this with externally generated topology and trajectory plus pull-coordinate, force, work, and replicate records.
- One pathway is not a mechanism. One pathway is not a mechanism. Address this with externally generated topology and trajectory plus pull-coordinate, force, work, and replicate records.
Steered molecular dynamics methods
A moving harmonic restraint is often attached to a distance or projected coordinate. The pulling speed and spring constant set how abruptly the system is driven, while atom-group definitions and reference motion determine what the coordinate actually measures.
Jarzynski-type free-energy estimates require appropriate work definitions and an adequate ensemble of trajectories. A peak force from one fast pull should not be reported as an equilibrium binding affinity or directly compared across unmatched protocols.
Steered molecular dynamics applications
Steered molecular dynamics is best suited to forced unbinding, unfolding, separation, and pathway hypotheses. Match the modeled system, timescale, resolution, and ensemble to the observable rather than choosing a protocol because it produces a longer trajectory or more elaborate figure.
Use simulation as model-based evidence. Connect trajectory observations to experimental data, alternative parameterizations, independent starts, and uncertainty whenever the downstream claim concerns mechanism, affinity, kinetics, stability, or population.
How to run steered molecular dynamics online
The connected workflow is a post-run review workflow. Generate the scientific simulation externally, preserve its method-native records, then upload compatible files for complementary structural analysis.
- Define pulling. Record pulled and reference groups, coordinate, direction, spring constant, velocity, and boundary handling.
- Run externally. Equilibrate starting states and execute independent steered simulations in a suitable external engine.
- Upload trajectory. Upload a compatible TPR topology and XTC trajectory to the review workflow.
- Review response. Inspect structural response beside the external force, extension, and work traces.
- Compare replicates. Compare pathways and summary statistics across replicates before drawing mechanistic conclusions.
How to interpret steered molecular dynamics results
Align structural events to the external force and extension traces: contact rupture, hydration changes, domain rotation, secondary-structure loss, and coordinate discontinuities may explain peaks. Check periodic boundaries and reference-group motion before assigning an event.
Report distributions across independent replicates, not only the smoothest trajectory. Distinguish reproducible intermediates from path-specific fluctuations and state how starting structures were selected.
How steered molecular dynamics works
Upload a compatible topology and trajectory from an external steered run for RMSD, RMSF, distance, and compactness review.
- Define pulling. Record pulled and reference groups, coordinate, direction, spring constant, velocity, and boundary handling.
- Run externally. Equilibrate starting states and execute independent steered simulations in a suitable external engine.
- Upload trajectory. Upload a compatible TPR topology and XTC trajectory to the review workflow.
- Review response. Inspect structural response beside the external force, extension, and work traces.
- Compare replicates. Compare pathways and summary statistics across replicates before drawing mechanistic conclusions.
Inputs and outputs
Check formats before running, then inspect and download the result from every workflow step.
Inputs
- Simulation evidence.
PDBmmCIFTPRGROXTCA compatible TPR topology and XTC trajectory plus external pull-coordinate, force, work, and protocol files.
Outputs
- Simulation outputs.
XTCPDBCSVJSONZIPStructural trajectory metrics for review; pulling forces, work profiles, and free-energy treatment remain external.
Tools for steered molecular dynamics
Use these methods to prepare inputs, run the core analysis, inspect outputs, and validate the evidence described in this workflow.
GROMACS
Run conventional protein molecular dynamics with classical force fields
MD Trajectory Analysis
Analyze compatible trajectories with structural and dynamical metrics
RMSD calculator
Compare representative structures with RMSD
Radius of gyration
Measure compactness for representative structures
pyRMSD
Calculate pairwise RMSD matrices for exported structure ensembles
DSSP
Assign secondary structure to representative protein conformations
SASA calculator
Calculate solvent-accessible surface area for exported structures
PDBFixer
Repair missing atoms and standardize structures before simulation
PDB2PQR
Prepare protonation, charges, and radii for structural review
PROPKA 3
Estimate pKa values and inspect protonation-sensitive sites
MolProbity
Validate representative protein conformations
Ramachandran plot
Inspect backbone dihedral quality in exported conformations
Other molecular dynamics workflows
Compare related approaches based on the molecular system, available evidence, required inputs, and decision you need to support.
Coarse-grained molecular dynamics
Groups atoms into interaction sites to access larger systems and longer effective timescales.
Replica exchange molecular dynamics
Runs interacting replicas at different temperatures or Hamiltonians and periodically attempts exchanges.
Protein molecular dynamics simulation
Simulates a solvated protein with a classical force field to study stability, flexibility, and conformational change.
All-atom molecular dynamics
Represents individual atoms explicitly under an atomistic force field and integration scheme.
Enhanced sampling molecular dynamics
Uses biasing or generalized-ensemble methods to cross barriers that conventional trajectories rarely traverse.
Frequently asked questions
A compatible TPR topology and XTC trajectory plus external pull-coordinate, force, work, and protocol files.
Structural trajectory metrics for review; pulling forces, work profiles, and free-energy treatment remain external.
Not currently. The simulation must be generated with a suitable external engine. ProteinIQ can review compatible topology and trajectory files with MDAnalysis-based structural metrics, while method-specific logs, bias, forces, exchange statistics, or reweighting remain external.
There is no universal number. Use independent starts and enough sampling to evaluate the slow observables behind the claim. Report replicate-level results, blockwise stability, and uncertainty rather than pooling trajectories without checking agreement.
Retain engine version, topology, coordinates, pulled groups, restraint geometry, spring constant, velocity, random seeds, force and work files, and every replicate.
A complete steered molecular dynamics project is commonly quote-based because system preparation, parameterization, sampling length, replica count, analysis, and interpretation vary substantially. Current published examples span from $50 for a bounded 100 ns GROMACS simulation to a $5,000 minimum for a dedicated commercial molecular-dynamics engagement.
Those prices describe materially different deliverables, so compare the included preparation, validation, replicates, analysis, raw files, interpretation, and support—not only trajectory length. Membrane building, unusual residues or ligands, advanced sampling, and convergence assessment can dominate the real scope.
ProteinIQ self-service starts at $29 per month for academic Plus and $99 per month for commercial Pro, with the configured run estimated in credits before submission. Done-for-you molecular dynamics work is scoped separately when preparation, method design, external advanced sampling, or interpretation is required.
Start with a workflow you can inspect and edit
Add your inputs, review the settings, and keep every structure, score, table, and file connected to the step that produced it.