CHARMM c30b1 hbuild.doc



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                 Construction of hydrogen positions

                   By Axel Brunger, December 1983

* Menu:

* Syntax::              Syntax of the HBUILD command
* Algorithm::           Description of the used algorithm


File: Hbuild ]-[ Node: Syntax
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                    Syntax of the HBUILD command

[SYNTAX HBUILD]

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 *note selection:(select.doc).).
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 (*note
hbonds:(hbonds.doc)Syntax.) for the detailed syntax, and
non-bond-spec are non-bonded interaction specifications, see (*note
nbonds:(nbonds.doc)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.


File: Hbuild ]-[ Node: Algorithm
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                    Alogorithm of the hydrogen builder


1. 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 comparisions 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.


2.  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:
a) proton bound to a donor with at least two heavy donor antecedents
    (e.g. (C, CA)-N-H)
b) proton bound to a donor with one heavy donor antecedent and no
    other proton (e.g. -OH-HH of tyrosine)
c) proton bound to a donor with one heavy donor antecedent and one
    other proton (e.g. -NH2-(HH21, HH22) group of arginine)
d) 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.
 a) water able to form two different hydrogen bonds to acceptor atoms
 b) water able to form only one hydrogen bond to acceptor atom
 c) 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.



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