QM/MM
TeraChem supports additive electrostatically embedded QM/MM calculations for all run modes (single point, gradient, frequency, optimizations, ab initio dynamics). Details of the implementation are provided in the theory subsection
TeraChem imeplements four distinct QM/MM workflows. They differ in which MM engine is used and which program drives the simulation:
| Mode | MM engine | Driver | Best for |
|---|---|---|---|
| Internal water QM/MM | TeraChem's built-in water force fields | TeraChem | Microsolvation studies with a QM solute and explicit MM waters |
| OpenMM with Amber input files | OpenMM (linked in TeraChem) | TeraChem | General QM/MM with arbitrary Amber-formatted topologies — the recommended TeraChem-driven QM/MM workflow |
| TeraChem/Amber Protocol-Buffers (TCPB) | Amber's MM engine | Amber | QM/MM driven by Amber, when access to Amber's full simulation machinery is needed |
| TeraChem/Amber file-based interface | Amber's MM engine | Amber | Same use case as TCPB but slower; prefer TCPB |
In the first two modes the MD trajectory is integrated by TeraChem. In the last two modes the trajectory is integrated by Amber, which calls TeraChem only to obtain the QM energies and gradients. See the Amber manual for instructions on configuring those Amber-driven modes.1
Amber-driven modes (TCPB and file-based)
When the simulation is driven by Amber, TeraChem acts purely as an energy and gradient server.
TCPB protocol-buffers interface
TeraChem speaks a client-server Protocol Buffers protocol with Amber that provides full access to Amber's QM/MM features while taking advantage of TeraChem's GPU acceleration.2 Setup is documented in the Amber manual.1 This is the recommended Amber-driven mode.
File-based interface
A simpler file-based interface (Amber writes a coordinate file, TeraChem reads it and writes energies and gradients) is also supported with Amber 12 or higher. This is slower than TCPB and not recommended for new work, but it is present for environments where the protobuf interface is not available.1
TeraChem-driven modes
When TeraChem drives the trajectory, the MM engine is chosen by which set of keywords is used in the input file:
- Setting
qmmm <file.xyz>activates the built-in water force fields. - Setting
prmtopandqmindicesactivates the OpenMM/Amber driver, which is far more flexible and is the recommended choice for any QM/MM beyond pure-water microsolvation.
These two QM/MM keyword sets are mutually exclusive.
Constrained QM/MM (FlexiBLE)
A common difficulty in QM/MM dynamics arises when the QM and MM regions are chemically identical — typically a QM solute plus its first solvation shell, surrounded by a much larger MM solvent bath. Without a constraint, molecules will diffuse across the QM/MM boundary during a trajectory and the partition will break down. TeraChem provides the FlexiBLE method,3 a constrained QM/MM formulation that preserves QM/MM identity while reproducing canonical-ensemble averages. See FlexiBLE for details; FlexiBLE is layered on top of the OpenMM/Amber driver.