Structure
Does the protein remain stable? Does the complex compact or expand? Do helices, sheets, or loops change?
Molecular dynamics 101
MD is a movie of molecular motion, built from physics.
A protein-ligand structure is a starting pose. Molecular dynamics asks how that pose behaves when atoms are allowed to move under a force field, temperature, pressure, water, ions, and time.
The core idea
Molecular dynamics treats atoms as particles. A force field estimates the energy of the system, the MD engine converts those energies into forces, and the simulation integrates motion in tiny time steps.
Mental model: docking gives you a pose; MD asks whether that pose can remain physically plausible while the environment pushes back.
The standard MD workflow
Prepare
Parameterize
Minimize
Equilibrate
Produce
Analyze
Preparation fixes structural problems and builds topology. Minimization relaxes bad contacts. NVT equilibration stabilizes temperature. NPT equilibration stabilizes pressure and density. Production MD generates the trajectory used for scientific interpretation.
Where scientific judgment enters
Automation helps, but MD still depends on meaningful choices: protonation state, retained cofactors, ligand parameters, force-field family, box size, salt concentration, simulation length, equilibration protocol, and analysis cutoffs.
PyMACS exposes these choices with defaults for beginners and command-line controls for experienced users.
Questions MD can help answer
Binding
Does the ligand stay in the pocket? Which residues contact it repeatedly? Which contacts are transient?
Mechanism
Do interactions cluster around a known motif? Does a cofactor or partner chain reshape the interface?
Comparison
Do two ligands, mutations, species, or apo/holo states produce different stability or contact patterns?