Example: Learning Unknown Equilibrium Parameters from Coordinates

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Example: Learning Unknown Equilibrium Parameters from Coordinates

In the following example, a protein and ligand are considered. The molecular structure of the the protein and the ligand have to be generated as outlined in Sections 3.7 and 3.13. The ligand requires the definition of the topology, e.g.,

topology
   autogenerate angles=true dihedrals=false end
   residue LIGA
      atom A type=C end
      atom B type=C end
      atom C type=C end
      atom D type=O end
      bond A B
      bond B C
      bond C D
   improper A B C D
   end
end

segment
   name=LIGA
   molecule number=1 name=LIGA end
end

Note that mass statements may be required if the atom types of the ligand are non-standard.

The protein parameters can be obtained from one of X-PLOR's protein parameter files. In general, the ligand parameters will be unknown. Suppose that the ligand coordinates are known from an appropriate crystal structure. We can learn the unknown ligand parameters from the known Cartesian coordinates. For purposes of structure determination, it is usually sufficient to set the energy constants to a uniform value.

The following statements define the unknown ligand parameters. They should be inserted in all X-PLOR protocols at any place after the molecular structure and coordinate files have been read and before the first energy evaluation is performed. These statements must also be inserted just before the hbuild statement in the molecular structure generation protocol (Section 3.13).

                  {*Learn bond, bond angle, and improper angle parameters.*}
flags exclude * include bonds angles impropers end
parameters
    learn initiate sele=(segid LIGA) mode=nostatistics end
    learn accumulate end
    learn terminate end
end

                                               {*Set the energy constants.*}
parameters
   BOND   (segid LIGA) (segid LIGA) 400. TOKEN
   ANGLE  (segid LIGA) (segid LIGA) (segid LIGA) 60. TOKEN
   IMPR  (segid LIGA) (segid LIGA) (segid LIGA) (segid LIGA) 50. TOKEN TOKEN

                         {*Set the nonbonded parameters (only if required).*}
   NBON ( (name A or name B or name C) and segid "LIGA" )  0.1 3.5 0.1 3.5
   NBON ( name D and segid "LIGA" )  0.1 3.4 0.1 3.4
end

                                            {* activate other energy terms *} 
flags include vdw elec pvdw pele end.

Note that the learn statement automatically sets the periodicity of all learned dihedral and improper angles to zero. Also note that the user has to specify improper and dihedral angles in the topology definition of the ligand (see above) in order to maintain planarity and chirality in certain parts of the ligand. Nonbonded parameters may have to be set by appropriate parameter statements unless they are already defined through type-based parameters. Finally, one has to activate the nonbonded energy terms and any other energy terms that might be needed, using the flags statement.

Xplor-NIH 2025-03-21