How to use peak mapping


MELD allows for the sampling of peak assignments, which is refered to as mapping. This is typically used for NMR experiments, where we have a series of peaks. Each peak corresponds to a group of atoms.

We know the peaks and we know the groups of atoms they may be assigned to, but we don’t know the actual assignment. We sample the possible assignments using Metropolis Monte Carlo, which provides the assignments that are in best agreement with the restraints (derived from data) and the force field.

For concreteness, we will consider the case of paramagnetic relaxation enhancement data, where each peak is either attenuated or not, depending on its proximity to a paramagnetic spin label.

Creating mappers

First, we need to create one or more mappers:

mapper = system.create_map("hsqc", n_peaks=100, atom_names=["H", "N"])

You can add as many mappers as you like. For example, there might be one for each chain if the NMR experiments were done in a way that resolves the peaks for each chain separately.

Each mapper requires a name, hsqc in the example. The name must be unique, but otherwise is not important.

The number of peaks must be defined. In this case 100, ranging from 0 to 99, inclusive.

Finally, the list of atom names associated with each peak must be specified. Since this is an HSQC spectrum, we defined N and H, but the atoms listed here don’t need to correspond only to the NMR experiment. For example, below we only use the amide proton, so atom_names=["H"] would have sufficed. Alternatively, we could have also included an additional atom, e.g. atom_names=["N", "H", "CA"].

Adding atom groups

Next, we must add all of the possible atom groups that could be assigned to the peaks:

# residue 1
    N=system.index.atom(0, "N"),
    H=system.index.atom(0, "H")
# residue 2
    N=system.index.atom(1, "N"),
    H=system.index.atom(1, "H")
# ...

Normally, one would use a for loop to add the atom groups. Each call to add_atom_group must have arguments that match atom_names from create_map. The values must be AtomIndex, which are conveniently returned by MELD’s indexing functions.

Each group of atoms is potentially assigned to exactly one peak. Importantly, all of the atoms in the group are assigned together, so in the example abovel the N and H from residue 1 will always be assigned together, and so on.

Mismatch between the number of peaks and atom groups

The number of atom groups and peaks does not need to match.

As explained below, peaks can be used to define restraints. When the number of atom groups is greater than the number of peaks, there will be some left over atom groups that are unassigned. These unassigned atom groups will simply not be involved in restraints, and thus will not contribute to the energy of the system.

When the number of peaks is larger than the number of residues, the situation is slighly more complex. In this case, there will be some peaks that do not map to anything. Any restraints involving those peaks will be treated specially by MELD, such that they do not contribute to the energy of the system.

Using peaks in restraints

Peak mapping is currently only supported for DistanceRestraint. When defining a distance restraint, peak mapping can be used to define either of the atoms involved, rather than specifying a fixed atom index.

For example, consider that peak zero was attenuated when a spin label was placed on residue 42. In this case we would have a distance restraint that favors short distances between whatever peak 0 mapps to and residue 42:

r1 = system.restraints.create(
    atom1=mapper.get_mapping(peak_id=0, atom_name="H"),
    atom2=system.index.atom(42, "CA"),
    r1=0 * u.nanometer,
    r2=0 * u.nanometer,
    r3=1.5 * u.nanometer,
    r4=1.7 * u.nanometer,
    k=2500 * u.kilojoule_per_mole / u.nanometer **2

On the other hand, consider that peak two was not attentuated. We would include a restraint that favors large distances between whatever peak two maps to and residue 42:

r2 = system.restraints.create(
    atom1=mapper.get_mapping(peak_id=1, atom_name="H"),
    atom2=system.index.atom(42, "CA"),
    r1=1.3 * u.nanometer,
    r2=1.5 * u.nanometer,
    r3=999 * u.nanometer,
    r4=999 * u.nanometer,
    k=2500 * u.kilojoule_per_mole / u.nanometer **2

The restraints must, of course, be added to the system. For example, as always active:

system.restraints.add_as_always_active_list([r1, r2])

Sampling assignments

Finally, the sample assignments, one must set the mapping_mcmc_steps parameter of the RunOptions object. This will perform the specified number of MCMC steps after each round of molecular dynamics.