Volume 1 Chapter 7 Geometric Surveys of Non-Bonded Fragments

A complete set of subfragments, linked together by non-bonded contacts, once located, can be treated in the same way as a bonded fragment. Thus, we may use the 3D-CONSTRAIN sub-menu to SETUP geometric objects, DEFINE and name geometrical parameters, TRANSFORM those parameters, and SELECT some subset of hits on the basis of geometrical parameter values.

The calculation of such geometric data is common in the systematic study of hydrogen bond interactions.

Ex. 11 We extend the study of amino-thiocarbonyl hydrogen bonding begun in Ex. 7 of section 7.14.3 to:

Calculate the S...H distance, the N-H...S angle and the spherical polar coordinates that relate the H...S vector to the expected lone pair plane of the sulfur atom (*LP2; a similar construct exists for studying lone-pair directionality at sp3 centres: *LP3, see Volume 2).
Select only those non-bonded fragments which have an N-H...S valence angle between 120 degrees and 180 degrees.
Tabulate and average all geometric parameters for all non-bonded fragments that survive the INTER search and angular SELECTion criterion.
```
VDW  TOL 0.0
CONTACT INTER 1 A 3 A
DEFINE HBOND 1 3
DEFINE HANG 2 1 3
DEFINE *LP2 THETA PHI 5 4 3 1
SELECT HANG 120.0 180.0
```

The setup of the search in the 3D-CONSTRAIN sub-menu and an example hit, and the summary statistics of all hits are given are shown below.

NFRAG   REFCOD     HBOND    HANG   THETA     PHI
     1  ABHYTZ     2.480 164.762 -20.906-106.093
     2  ACRTUR     2.589 157.488  32.379 106.570
     3  ACRTUR     2.561 170.452  -7.296-105.989
     4  ACTCBZ     2.931 137.567  46.311 121.393
   685  XANHYD     2.112 160.436  17.513 101.275
   686  XANHYD01   2.138 160.395 -18.660 100.561
   687  ZNDITZ02   2.856 124.215  34.757-151.824
   688  ZZZEII01   2.890 157.984 -54.200 160.643
   689  ZZZGEO01   2.546 169.119  -6.861-109.372
   690  ZZZMJK02   2.634 155.342 -17.372 108.877
   691  ZZZQMK10   2.520 140.496 -71.513 132.202
        Nobs         691     691     691     691
        Mean       2.604 156.226  -2.651  -5.224
        SDSample   0.176  14.416  38.270 111.815
        SDMean     0.007   0.548   1.456   4.254
        Minimum    2.058 120.578 -85.672-179.076
        Maximum    2.997 179.169  85.205 179.849

7.14.8 Efficiency of Non-Bonded Searches

It is obvious that the intermolecular non-bonded search mechanism is highly cpu-intensive, since it can involve the testing of an appreciable number of symmetry/translational variants of atomic positions. Even though the symmetry/translation search routine employs upper-bound tests and is as efficient as possible, the intermolecular searches are likely to take much longer than any comparable intramolecular search.

In the present database and software release, no 3D screening system exists to speed these intermolecular searches. The only screening procedures employed relate to the 2D chemical structures of the subfragments that make up the complete non-bonded search query. This lack of 3D intermolecular distance screens is currently being remedied.

For the present, several factors should be considered when composing non-bonded searches:

Choose distance criteria carefully. Remember that the search space is proportional to the third power of the distance.
The larger the 2D subfragments, the greater the possibility for generating a reasonable number of 2D screens.
Incorporate user-defined screens whenever possible. For example, restrict the search to entries that are error-free, not disordered, have R-factors below some cut-off value, or are drawn from just the organic (or metallo-organic) sections of the database only.
CONTACTs that use GROUPs are searched more quickly by centroid representations than by atom-by-atom methods.
Exercise care when conducting searches with common functional groups, e.g. C=O, N-H, and aromatic rings. Conduct a quick 2D search to determine the number of entries that contain the subfragments that will be used in the nonbonded search. If the number is large consider limiting the non-bonded search to a particular class of entries as a first pass.
Subfragments that have a high degree of topological symmetry (e.g. rings) will take longer in exhaustive searches.

Back to Table of Contents

Volume 1 Chapter 7 Further Examples of Non-Bonded Searches .

7.14.7 Geometrical Surveys of Non-Bonded Fragments

7.14.8 Efficiency of Non-Bonded Searches