Xplor-NIH for molecular structure determination from NMR and other data sources

Abstract

Xplor-NIH is a popular software package for biomolecular structure determination from nuclear magnetic resonance (NMR) and other data sources. Here, some of Xplor-NIH's most useful data-associated energy terms are reviewed, including newer alternative options for using residual dipolar coupling data in structure calculations. Further, we discuss new developments in the implementation of strict symmetry for the calculation of symmetric homo-oligomers, and in the representation of the system as an ensemble of structures to account for motional effects. Finally, the different available force fields are presented, among other Xplor-NIH capabilities.

Keywords: NMR restraints; SAXS; computational toolbox; cryo-electron microscopy; nucleic acid; optimization; protein; structure determination.

Figure 1

Topology setup for torsion angle dynamics with a grouped region composed of residues numbered from 100 to 120, inclusive.

Figure 2

Loading PSF information from a file, or generating it from sequence. protein.psf would contain a pre‐calculated PSF file, while protein.seq would contain a list of whitespace‐separated 3‐character residue names. PSF information is required for any Xplor‐NIH functionality which references atomic coordinates.

Figure 3

Schematic of a structure calculation script.

Figure 4

Setup of the energy term for refining against an atomic probability density map (e.g., generated from cryo‐electron microscopy).

Figure 5

Setup of the RepelPot energy term for atom‐atom repulsion with the correct radius scale factor set automatically. This setup specifies that only interactions between residues 2–40 and 50–90 are computed. This setting can speed up non‐bonded calculations when regions are grouped as rigid bodies.

Figure 6

Instantiating the dihedral portion of the default force field using TorsionDBPot and Terminal14Pot for dihedral angles which contain one or more protons (see text).

Figure 7

An example of how to include the EEFx energy term. The initEEFx function loads the appropriate electrostatic, non‐bonded and solvation parameters, while the eefxpot object is instantiated later in a script with other energy terms.

Figure 8

Example of generating a second subunit related by a ${180}^{°}$ rotation about the z axis relative to the protomer. The segment name of the second subunit is set to “B” while that of the first subunit is set to “A”.

Figure 9

At the end of the calcOneStructure function introduced in Figure 3, add this call to write out the coordinates of all subunits with the suffix .full. symSim is the SymSimulation object created in Figure 8.

Figure 10

Code to create a three‐membered ensemble. Creation of the EnsembleSimulation makes copies of the current atom positions, velocities, and so forth. The constituent structures do not interact except by special ensemble‐aware energy terms. The sum averaging setting specifies that energies (including kinetic energy) increase in proportion to the ensemble size.

Figure 11

The pop object contains a description of the populations of a three‐state symmetric dimer with two substates in each subunit. The minimal population is set to be $0.1/N_e$. The pop object is also an energy term, implementing the regularizing energy defined in Eq. (10).

Figure 12

Examples of reading and writing NEF formatted files. The readNef function will generate PSF information, and additional energy terms can be initialized using content in the cifData object. Here, coordinates are read in mmCIF format. For writing a NEF file the genHeader function will generate connectivity information and the noePotTools.writeNEF will then add restraint data from noe, an NOEPot object defined previously in the script (not shown).