# Molecule definition¶

## Moleculetype entries¶

An organizational structure that usually corresponds to molecules is the [ moleculetype ] entry. This entry serves two main purposes. One is to give structure to the topology file(s), usually corresponding to real molecules. This makes the topology easier to read and writing it less labor intensive. A second purpose is computational efficiency. The system definition that is kept in memory is proportional in size of the moleculetype definitions. If a molecule is present in 100000 copies, this saves a factor of 100000 in memory, which means the system usually fits in cache, which can improve performance tremendously. Interactions that correspond to chemical bonds, that generate exclusions, can only be defined between atoms within a moleculetype. It is allowed to have multiple molecules which are not covalently bonded in one moleculetype definition. Molecules can be made infinitely long by connecting to themselves over periodic boundaries. When such periodic molecules are present, an option in the mdp file needs to be set to tell GROMACS not to attempt to make molecules that are broken over periodic boundaries whole again.

## Intermolecular interactions¶

In some cases, one would like atoms in different molecules to also interact with other interactions than the usual non-bonded interactions. This is often the case in binding studies. When the molecules are covalently bound, e.g. a ligand binding covalently to a protein, they are effectively one molecule and they should be defined in one [ moleculetype ] entry. Note that pdb2gmx has an option to put two or more molecules in one [ moleculetype ] entry. When molecules are not covalently bound, it is much more convenient to use separate moleculetype definitions and specify the intermolecular interactions in the [ intermolecular_interactions] section. In this section, which is placed at the end of the topology (see Table 13), normal bonded interactions can be specified using global atom indices. The only restrictions are that no interactions can be used that generates exclusions and no constraints can be used.

## Intramolecular pair interactions¶

Extra Lennard-Jones and electrostatic interactions between pairs of atoms in a molecule can be added in the [ pairs ] section of a molecule definition. The parameters for these interactions can be set independently from the non-bonded interaction parameters. In the GROMOS force fields, pairs are only used to modify the 1-4 interactions (interactions of atoms separated by three bonds). In these force fields the 1-4 interactions are excluded from the non-bonded interactions (see sec. Exclusions).

[ pairtypes ]
; i    j func         cs6          cs12 ; THESE ARE 1-4 INTERACTIONS
O    O    1 0.22617E-02   0.74158E-06
O   OM    1 0.22617E-02   0.74158E-06
.....


The pair interaction parameters for the atom types in ffnonbonded.itp are listed in the [ pairtypes ] section. The GROMOS force fields list all these interaction parameters explicitly, but this section might be empty for force fields like OPLS that calculate the 1-4 interactions by uniformly scaling the parameters. Pair parameters that are not present in the [ pairtypes ] section are only generated when gen-pairs is set to yes in the [ defaults ] directive of forcefield.itp (see Topology file). When gen-pairs is set to no, grompp will give a warning for each pair type for which no parameters are given.

The normal pair interactions, intended for 1-4 interactions, have function type 1. Function type 2 and the [ pairs_nb ] are intended for free-energy simulations. When determining hydration free energies, the solute needs to be decoupled from the solvent. This can be done by adding a B-state topology (see sec. Free energy calculations) that uses zero for all solute non-bonded parameters, i.e. charges and LJ parameters. However, the free energy difference between the A and B states is not the total hydration free energy. One has to add the free energy for reintroducing the internal Coulomb and LJ interactions in the solute when in vacuum. This second step can be combined with the first step when the Coulomb and LJ interactions within the solute are not modified. For this purpose, there is a pairs function type 2, which is identical to function type 1, except that the B-state parameters are always identical to the A-state parameters. For searching the parameters in the [ pairtypes ] section, no distinction is made between function type 1 and 2. The pairs section [ pairs_nb ] is intended to replace the non-bonded interaction. It uses the unscaled charges and the non-bonded LJ parameters; it also only uses the A-state parameters. Note that one should add exclusions for all atom pairs listed in [ pairs_nb ], otherwise such pairs will also end up in the normal neighbor lists.

Alternatively, this same behavior can be achieved without ever touching the topology, by using the couple-moltype, couple-lambda0, couple-lambda1, and couple-intramol keywords. See sections sec. Free energy calculations and sec. Free energy implementation for more information.

All three pair types always use plain Coulomb interactions, even when Reaction-field, PME, Ewald or shifted Coulomb interactions are selected for the non-bonded interactions. Energies for types 1 and 2 are written to the energy and log file in separate “LJ-14” and “Coulomb-14” entries per energy group pair. Energies for [ pairs_nb ] are added to the “LJ-(SR)” and “Coulomb-(SR)” terms.

## Exclusions¶

The exclusions for non-bonded interactions are generated by grompp for neighboring atoms up to a certain number of bonds away, as defined in the [ moleculetype ] section in the topology file (see Topology file). Particles are considered bonded when they are connected by “chemical” bonds ([ bonds ] types 1 to 5, 7 or 8) or constraints ([ constraints ] type 1). Type 5 [ bonds ] can be used to create a connection between two atoms without creating an interaction. There is a harmonic interaction ([ bonds ] type 6) that does not connect the atoms by a chemical bond. There is also a second constraint type ([ constraints ] type 2) that fixes the distance, but does not connect the atoms by a chemical bond. For a complete list of all these interactions, see Table 14.

Extra exclusions within a molecule can be added manually in a [ exclusions ] section. Each line should start with one atom index, followed by one or more atom indices. All non-bonded interactions between the first atom and the other atoms will be excluded.

When all non-bonded interactions within or between groups of atoms need to be excluded, is it more convenient and much more efficient to use energy monitor group exclusions (see sec. The group concept).