# Your first simulation: DHFR

**You will learn:** how to run an NVT molecular-dynamics simulation of [dihydrofolate reductase](https://en.wikipedia.org/wiki/Dihydrofolate_reductase) (DHFR) — a small globular protein widely used as an MD benchmark — from prepared force-field files, both from the command line and from Python. The same system is shown with CHARMM and AMBER topologies side-by-side; pick whichever your build pipeline produces.

**Prerequisites:**

- ACEMD installed (see [Installation](../installation.md)).
- An NVIDIA GPU with CUDA-capable drivers, or any GPU with OpenCL.
- The benchmark files: {download}`acemd_benchmarks.zip <../acemd_benchmarks.zip>`.

## Step 1 — Unpack the benchmark files

Extract the archive and switch into the directory matching your force field:

::::{tab-set}

:::{tab-item} CHARMM

```bash
unzip acemd_benchmarks.zip -d /tmp/
cd /tmp/acemd_benchmarks/dhfr_charmm
```

The directory contains a PSF topology (`dhfr.psf`), a `.prm` parameter file, a starting PDB, and an `input.yaml`.
:::

:::{tab-item} AMBER

```bash
unzip acemd_benchmarks.zip -d /tmp/
cd /tmp/acemd_benchmarks/dhfr_amber
```

The directory contains a PRMTOP topology (`dhfr.prmtop`) — which carries both topology and parameters — a starting PDB, and an `input.yaml`.
:::

::::

## Step 2 — Inspect the input file

::::{tab-set}

:::{tab-item} CHARMM

```{code-block} yaml
:caption: input.yaml

parameters: dhfr.prm
structure: dhfr.psf
coordinates: dhfr.pdb
boxsize: [62.23, 62.23, 62.23]
thermostat: true
run: 28ns
```

- `structure` / `parameters` — CHARMM topology + force-field parameters.
- `coordinates` — starting positions (the topology has no coordinates).
- `boxsize` — orthogonal box, 62.23 Å on a side.
- `thermostat: true` — turn on the Langevin thermostat at the default 298.15 K.
- `run: 28ns` — total simulation time. Time units (`fs`, `ps`, `ns`, `us`) or a raw integer step count are both accepted.
:::

:::{tab-item} AMBER

```{code-block} yaml
:caption: input.yaml

structure: dhfr.prmtop
coordinates: dhfr.pdb
boxsize: [62.23, 62.23, 62.23]
thermostat: true
run: 28ns
```

- `structure` — PRMTOP carries both topology and parameters, so there's no separate `parameters` line.
- `coordinates` — starting positions.
- `boxsize` — orthogonal box, 62.23 Å on a side.
- `thermostat: true` — turn on the Langevin thermostat at the default 298.15 K.
- `run: 28ns` — total simulation time.
:::

::::

Everything else is left at the default — see [Input options](../reference/input-options.md) for the full list.

The default time step is 4 fs, which auto-enables hydrogen-mass repartitioning and bond constraints — see [Integrator and constraints](../explanation/integrator-and-constraints.md) for why.

## Step 3 — Start the simulation

From inside the directory:

```bash
acemd
```

By default ACEMD runs on GPU device 0. To pick a different device, or to use multiple GPUs, see [Select GPU devices](../how-to/select-gpu-devices.md).

While the run progresses ACEMD streams a log to stdout and writes the same values to `output.csv`. Trajectory frames go to `output.xtc`, and a binary checkpoint is written to `restart.chk` every `trajectoryperiod` steps so you can resume on the same hardware.

## Step 4 — Inspect the output

After the run completes the directory contains the original input files plus:

```text
output.coor  output.csv   output.vel   output.xsc   output.xtc   restart.chk
```

- `output.coor`, `output.vel`, `output.xsc` — final positions, velocities, and box from the last frame.
- `output.xtc` — trajectory frames (unwrapped — atoms can drift outside the initial box; see [How to wrap a trajectory](https://software.acellera.com/moleculekit/howto/wrap-trajectories.html)).
- `output.csv` — energies, temperature, pressure, and timings per logged step.
- `restart.chk` — checkpoint for resuming with `restart: true`.

## Step 5 — Run it from Python instead

ACEMD 4.0 introduced a Python API. The {py:func}`~acemd.acemd.acemd` function takes a directory (the equivalent of `cd`-ing there) and any input-file option as a lowercase keyword:

```python
from acemd import acemd

acemd("/tmp/acemd_benchmarks/dhfr_charmm")  # or .../dhfr_amber
```

Keyword arguments override the on-disk `input.yaml` — useful for running a sweep without editing files:

```python
acemd("/tmp/acemd_benchmarks/dhfr_charmm", run="2ns")
```

CLI flags pass through with the same lowercased name:

```python
acemd("/tmp/acemd_benchmarks/dhfr_charmm", device=[0, 1], run="2ns")
```

## Where to go next

- Run a [hybrid NNP/MM simulation](../how-to/run-an-nnp-mm-simulation.md) on a small molecule of interest.
- Apply [positional restraints](../how-to/use-positional-restraints.md) during equilibration.
- Browse the full list of [input options](../reference/input-options.md).