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Generation of Hydrogen Bonds

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The HQBM Module of CHARMM

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Construction of hydrogen positions

By Axel Brunger, December 1983

Syntax of the HBUILD command

HBUILD     [atom-selection] hbond-spec  non-bond-spec

           [PHIStp real] [PRINt]  [CUTWater real]

           [WARN] [DISTof real] [ANGLon real]

where <atom-selection> specify the hydrogens to be (re-)constructed (see Atom Selection). By default (if no selection is specified) these are all unknown hydrogens and lone pairs (this is equivalent to a selection “SELEction (LONE .OR. HYDRogen) .AND..NOT INITial”).

hbond-spec are hydrogen bond specifications, see (Syntax.) for the detailed syntax, and non-bond-spec are non-bonded interaction specifications, see Syntax for the detailed syntax.

At present the use of the following options is not supported by HBUILD and may yield to errors:

  • BEST in hbond-spec,
  • GROUP [...] in non-bond-spec.
  • PHIStp (default: 10 degrees) determines the step size of the donor group rotation algorithm in HBUILD.
  • PRINt (default: PRINt flag off) if specified prints information about electrostatic, Van der Waals, hydrogen bond, dihedral energy as well as ST2 energy during the performance of the algorithm.

If WARN is specified routine ST2WRN is invoked after exiting HBUILD to provide information about unlikely water-(non-polar group) configurations. See that routine for the purpose of DISTof and ANGLon.

Any bond between atoms, both of which are to be built, will be ignored. If it is desired to build a chain of atoms with this method, it is essential to build each level in this chain with a separate HBUILD invocation.

Algorithm of the hydrogen builder

Introduction

In most cases a X-ray diffraction structure contains no information about the positions of the protons of a particular protein. However, our empirical hydrogen bond energy function CHARMM requires the treatment of explicit protons at least for hydrogen bond forming protons. To construct proton positions starting from the X-ray structure of a protein is the task of our method. At present only hydrogen bonding protons are constructed. Due to the generality of the algorithm also the positions of aliphatic protons could be easily constructed. Proton coordinates are constructed for the protein as well as for the surrounding water. The water requires special treatment and the investigations for a this part of the method are not yet complete.

The presented method was tested using the neutron diffraction structures of two different proteins systems each including several water molecules. One structure was ribonuclease A with 128 water molecules. The other structure was trypsin with 30 ordered water molecules. The knowledge of the proton positions using the neutron data allowed detailed comparisons of spatial positions of the protons, hydrogen bond and energy differences. The results indicate that the use of the presented method should yields to a good initial structure of the protons and is therefore a useful tool in cases where no neutron structure is available.

Methods

In the first part of our method all proton positions of the protein are constructed. The protons are classified according to their environment. At present the following classes are defined:

  1. proton bound to a donor with at least two heavy donor antecedents (e.g. (C, CA)-N-H)
  2. proton bound to a donor with one heavy donor antecedent and no other proton (e.g. -OH-HH of tyrosine)
  3. proton bound to a donor with one heavy donor antecedent and one other proton (e.g. -NH2-(HH21, HH22) group of arginine)
  4. proton bound to a donor with one heavy donor antecedent and two other protons (e.g. -NZ-(HZ1, HZ2, HZ3) group of lysine)

First, all protons of class a) are placed by using equilibrium bond lengths, angles and dihedrals. This problem is overdetermined if there exists more than one heavy donor antecedent. In these cases an averaging over all possible ways to place the proton is performed.

In the next step the protons of all other classes are constructed. All these classes have in common that there is a degree of freedom to place the protons (e.g. a spin around the CE-NZ bond of lysine). To find an optimum position the dihedral angle with the symmetry axis antecedent-donor is modified in small steps over a certain range determined by the symmetry of the donor group. For each dihedral angle the protons of the donor are placed according to their equilibrium geometry and the relative energy of the corresponding configuration is evaluated. The energy is determined by using the hydrogen bond potential, the Van der Waals term, electrostatic term and the dihedral term derived from the full energy expression of CHARMM. The dihedral with the lowest energy is taken and the protons of the donor group are placed with the optimum dihedral angle. This procedure is performed in the order given by the residue sequence of the protein. Not jet constructed protons have no influence on the current energy evaluations.

After construction of all explicit protein protons the water protons are constructed. First, a sequence of water molecules is determined independent of any input sequence (e.g. by the X-ray data). The waters are ordered in respect to the minimum distance of the water oxygen to any protein atom. The protons of waters near the protein are constructed first. At present there are three classes of water molecules treated in our method.

  1. water able to form two different hydrogen bonds to acceptor atoms
  2. water able to form only one hydrogen bond to acceptor atom
  3. water forms no hydrogen bonds at all to acceptor atoms.

In case a) protons are placed by performing a rotation of the water molecule in the plane defined by the two best hydrogen bonds and taking the minimum energy configuration. In case b) one proton is placed on the (linear) hydrogen bond and the water is rotated around this hydrogen bond axis placing the other proton using the equilibrium geometry. Again the minimum energy configuration is taken. The evaluated relative energy is the sum of the Van der Waals, the electrostatic and the hydrogen bond energy terms. Finally, the water protons of case b) are placed in a standard way (H1 on x-axis, H2 in x,y plane) after all other protons have been placed. ST2 water molecules are treated as regular waters for the proton construction. The position of the lone pairs is derived from the proton positions.