Biophysics 101

Understanding Energy Minimization

Energy Minimization is the process of moving atoms "downhill" to find the nearest stable shape.

      High Energy
      (Unstable)
          |
         / \       Forces push atoms "downhill"
        /   \     (Gradient Descent)
       /     \
      /       \___
     /            \
    /              \__ Low Energy
   /                  (Stable / Minimized)

synth-pdb defaults to Implicit Solvent (OBC2) to simulate the effect of water without the computational cost of thousands of explicit water molecules. This allows for lightning-fast physics refinement natively on the CPU.

Explicit Solvent (Water Box)

For advanced biophysics and molecular dynamics (MD), synth-pdb now fully supports generating and simulating Explicit Solvent.

By using --solvent explicit, OpenMM will build a surrounding box of classical TIP3P water molecules around the generated peptide.

# Generate a linear peptide padded by 1.2 nanometers of water
synth-pdb --sequence ALA-PRO-GLY --minimize \
  --solvent explicit \
  --solvent-padding 1.2

[!TIP] Stripping Solvent: By default, synth-pdb strips the thousands of generated HOH (water) atoms from the final .pdb output to keep file sizes small and clean for downstream AI pipelines. If you want to export the entire simulated water box, use the --keep-solvent flag.

The Generation Pipeline

[User] -> [Generator] -> [Geometry Builder] -> [Sidechain Packer] -> [Energy Minimizer] -> [PDB File]
             ^                  |                    |                      |
             |              (N-CA-C-O)           (Rotamers)             (OpenMM)
             |                                       |                      |
             +---------------------------------------+----------------------+