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Chapter 33. Multi-atom probes
Each multi-atom Probe is identified by its "Probe Name". For example, the chemical formula of the anionic aliphatic carboxy Probe is CH2.COO- but its Probe Name is simply COO- The Probe Name is used to define the Probe when a GRID run is being prepared. It may be called from the Probe Menu in Programme GREAT, or entered by selecting from the 'Multi Atom' menu in Greater, or entered with the directives on a line by itself in the Command file for GRID.
33.1. The aliphatic carboxylate probe COO-
Recommended Probe Name: COO-
The complete carboxy anion group C.COO- has been calibrated as a multi-atom Probe. It is an anion consisting of two sp2oxygen atoms bonded to the sp2 carboxy carbon, which is itself bonded to another (beta) carbon atom in a CH2 methylene group:
CH2 The beta methylene group | C The sp2 carboxy carbon / \ :O O: The two sp2 carboxy oxygen atoms " " |
This Probe contains four lone pairs which can accept upto four hydrogen bonds, correctly oriented with respect to each other and with respect to the four heavy atoms of the Probe. The Probe Name for this Probe is COO- (see note above)
The position of this Probe on the Grid is defined by one of its carboxy oxygen atoms. The oxygen is at the grid point, and at each step of the Grid computation the whole energy of the Probe is assigned to that one point. The other oxygen of the multi-atom Probe might well be making a strong hydrogen bond to an atom of the Target that was five or more Angstroms away from the grid point. Never-the-less all the hydrogen bond and other interaction energies of the whole multi-atom Probe are assigned to the current grid point at each stage of the computation.
The lineprinter output file from GRID explicitly defines the Target atoms to which the "other" oxygen of the multi-atom Probe makes its hydrogen bonds. Therefore, the procedure for modelling the carboxy group in relation to the Target should be:
Place one of the Probe oxygens at a strong energy minimum on the Grid map.
Identify the Target atoms (if any) to which the "other" oxygen makes hydrogen bonds. These atoms are specifically defined in the GRIDLONT lineprinter output file.
Move the "other" oxygen to a position at which it can make the appropriate hydrogen bonds. The estimated position of this "other" oxygen is also printed to the lineprinter output file GRIDLONT, but these coordinates have not been optimised by Grid.
Rotate the whole Probe around the axis defined by the oxygens, allowing the oxygens themselves to move a little if need be in order to optimise their positions, and thus identify the appropriate orientation of the Probe for the chosen Grid point.
33.2. The aromatic carboxylate probe AR.COO-
Recommended Probe Name: AR.COO-
The complete aromatic carboxy anion Probe AR.COO- is an anion consisting of two sp2 oxygen atoms bonded to the sp2 carboxy carbon, which is itself bonded to a planar aromatic ring system:
Ar The coplanar aromatic ring system | C The sp2 carboxy carbon / \ :O O: The two sp2 carboxy oxygen atoms " " |
It contains four lone pairs which can accept upto four hydrogen bonds, correctly oriented with respect to each other and with respect to the rest of the probe. The aromatic ring AR is coplanar with the carboxy group, and might represent the benzene ring of benzoic acid or the heterocyclic ring of nicotinic acid. It is not fully modelled in order to save processing time, but is simply treated as a solid object. This ensures that the carboxy group will not be squeezed into a Target site that is too small for a larger molecule, but any dispersive or electrostatic attraction between the AR group and the Target site is not modelled.
The Probe Name for this Probe is AR.COO- (see note above), and the position of the Probe on the Grid is defined by one of its carboxy oxygen atoms.
33.3. The aliphatic amide probe CONH2
Recommended Probe Name: CONH2
The aliphatic amide Probe CONH2 consists of one sp2 oxygen atom and one sp2 NH2 group, both of which are bonded to an sp2carbon which is itself bonded to another (beta) methylene group:
CH2 The beta methylene group
|
C The sp2 carbon
/ \
:O N--H The sp2 oxygen and NH2 groups
" |
H |
It contains two lone pairs which can accept and two hydrogens which can donate a total of four hydrogen bonds, all correctly oriented with respect to each other and with respect to the four Probe atoms. The Probe Name for this Probe is CONH2 (see note above).
For each grid point the Programme makes two distinct computations with an assymetric multi-atom Probe such as CONH2. First the sp2 oxygen is placed at the grid point, and the multi-atom Probe is fitted to the Target by rotating it to obtain the best fit, subject to the constraint that the oxygen remains at the grid point. The most favourable energy E1 is recorded, and the multi-atom Probe is then turned round and refitted with the nitrogen of the sp2 NH2 group at the same Grid point giving an energy E2. Thus E1 would be the most favourable energy with the oxygen at the grid point, and E2 with the nitrogen at the same position. A choice between E1 and E2 is then made, and the more favourable (i.e. the more negative) energy is finally chosen for that grid point.
The procedure for modelling such a Probe in relation to the Target should therefore begin by an examination of the lineprinter output file (GRIDLONT; see below) for the chosen grid point. This GRIDLONT file will explicitly show which Probe atom is at the grid point, and what hydrogen bonds are made by the "other" hydrogen-bonding group of the Probe:
THE FIRST H-BONDING ATOM OF THE PROBE IS AT THE GRID POINT.
THE SECOND PROBE ATOM MAKES THE H-BONDS TO TARGET ATOMS:
1426 1424 OE2 GLU A 190 AND 7126 7123 NE2 HIS B 452
THE SECOND HYDROGEN BONDING ATOM OF THE PROBE IS AT:
X = 27.254 Y = 9.736 Z = -17.693 |
33.4. The aromatic amide probe AR.CONH2
Recommended Probe Name: AR.CONH2
The aromatic amide Probe AR.CONH2 consists of one sp2 oxygen atom and one sp2 NH2 group, both of which are bonded to an sp2carbon which is itself bonded to a planar aromatic ring system:
AR The coplanar aromatic ring system
|
C The sp2 carbon
/ \
:O N--H The sp2 oxygen and NH2 groups "
|
H |
It contains two lone pairs which can accept and two hydrogens which can donate a total of four hydrogen bonds, all correctly oriented with respect to each other and with respect to the rest of the Probe. The Probe Name for this Probe is AR.CONH2 (see note above).
The aromatic ring AR is coplanar with the amide group, and might represent the benzene ring of benzamide or the heterocyclic ring of nicotinamide. It is modelled as described above for the aromatic carboxy multi-atom Probe AR.COO-. Two distinct computations are made at each grid point with this assymetric multi-atom Probe, as described above for the CONH2 aliphatic amide multi-atom Probe.
33.5. The aliphatic cis or trans amide probe CONHR
Recommended Probe Name: CONHR
The aliphatic amide Probe CONHR consists of one sp2 oxygen atom and one sp2 NHR group, both of which are bonded to an sp2carbon which is itself bonded to another (beta) methylene group:
CH2 The beta methylene group
|
C The sp2 carbon
/ \
:O N--R The sp2 oxygen and NHR groups
" |
H |
It contains two lone pairs which can accept and one hydrogen which can donate a total of three hydrogen bonds, all correctly oriented with respect to each other and with respect to the four Probe atoms. The Probe Name for this Probe is CONHR (see note above).
The NH moiety of this Multi-Atom Probe can be either cis with respect to the carbonyl oxygen as shown above, or it can be trans:
CH2 The beta methylene group
|
C The sp2 carbon
/ \
:O N--H The sp2 oxygen and NHR groups
" |
R |
and the choice between cis and trans MUST be specified by the User. The appropriate indicator should be included in the list of Directives before IEND and the job-title like this:
. . . CONHR CIS . . IEND Title of the job |
If the CIS or TRANS indicator is not specified, this Multi-Atom Probe will behave as if it had a complete NH2 moiety.
The procedure for modelling such a Probe in relation to the Target is as described above for the CONH2 Multi-Atom Probe.
33.6. The aromatic cis or trans amide probe AR.CONHR
Recommended Probe Name: AR.CONHR
The aromatic amide Probe AR.CONHR consists of one sp2 oxygen atom and one sp2 NHR group, both of which are bonded to an sp2carbon which is itself bonded to a planar aromatic ring system. It is similar to the previous two Multi-Atom Probes, and contains two lone pairs which can accept and one hydrogens which can donate a total of three hydrogen bonds, all correctly oriented with respect to each other and with respect to the rest of the Probe. Further description is not necessary, since the previous descriptions also apply to this AR.CONHR probe.
33.7. The aliphatic amidine probe AMIDINE
Recommended Probe Name: AMIDINE
The aliphatic amidine Probe consists of two sp2 NH2 groups, both of which are bonded to an sp2 carbon which is itself bonded to another (beta) methylene group:
CH2 The beta methylene group
|
C The sp2 carbon
/ \
H--N N--H The sp2 NH2 groups
| |
H H |
It contains four hydrogens which can donate a total of four hydrogen bonds, all correctly oriented with respect to each other and with respect to the four heavy atoms of the Probe. The Probe Name for this Probe is AMIDINE and it has a net electrostatic charge of +1.
The procedure for modelling such a Probe in relation to the Target is analogous to the procedure for a multi-atom carboxy Probe, as described above.
33.8. THe aromatic amidine probe AR.AMIDINE
Recommended Probe Name: AR.AMIDINE
The aromatic amidine Probe consists of two sp2 NH2 groups, both of which are bonded to an sp2 carbon which is itself bonded to a planar aromatic ring system:
AR The coplanar aromatic ring system
|
C The sp2 carbon
/ \
H--N N--H The sp2 NH2 groups
| |
H H |
It contains four hydrogens which can donate a total of four hydrogen bonds, all correctly oriented with respect to each other and with respect to the rest of the Probe. The Probe name for this Probe is AR.AMIDINE, and it has a net electrostatic charge of +1 on the amidine moiety.
The procedure for modelling such a Probe in relation to the Target is analogous to the procedure for a multi-atom carboxy Probe, as described above.
33.9. The meta-diamino-benzene probe
Recommended Probe Name: M-DIAMINE
The meta-diamino-benzene Probe consists of two sp2 NH2 groups, each of which is bonded to an sp2 carbon which is itself part of a simulated benzene ring:
NH2 The first sp2 NH2 group
|
C The first sp2 carbon
/ \
H--C C--H PROBE
| |
H--C C--NH2 The second sp2 NH2 group
\ / and its carbon
C
|
H |
It contains four hydrogens which can donate a total of four hydrogen bonds, all correctly oriented with respect to each other and with respect to the four heavy atoms of the Probe. The Probe Name for this Probe is M-DIAMINE and it has a net electrostatic charge of zero.
The procedure for modelling such a Probe in relation to the Target is analogous to the procedure for a multi-atom carboxy Probe, as described above.
MULTI-ATOM PROBE NAMES: Reasonable variations will be accepted for the name of a Multi-Atom Probe, but equivocal names will be rejected. The above names are recommended, because a variant name which is acceptable now might become equivocal in a later version of the Programmes, when more multi-atom Probes have been introduced. Thus the aromatic amidine Probe can be called AR_AMIDINE or AR-AMIDINE or aramidine in this Version of GRID, but some of these alternative names may become unacceptable later.
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