15.1.1. Type 0 (N1IN = 0)

Type 0 ATOMS and Type 0 HETATMS do not make hydrogen bonds. The following different cases, which are all transparent to the User, may occur:

• Type 0 HETATMS are not bonded directly to hydrogen. e.g. the HETATM C is a carbonyl carbon, and neither donates nor accepts a hydrogen bond.

• Type 0 ATOMS are not bonded directly to hydrogen. e.g. the ATOM C is a carbonyl carbon in amino-acids, and neither donates nor accepts a hydrogen bond.

• Type 0 EXTENDED atoms are usually at the centre of an extended group, in which one or more hydrogens are included. Thus the CB extended atom of alanine represents a whole CH3 methyl group in which none of the hydrogens makes a hydrogen bond.

15.1.2. Type 1. (N1IN=1)

This is a hydrogen-bonding hydrogen with, for example, the planar geometry of nitrogen NE1 in a tryptophan ring:

               C               (CA) the alpha-carbon atom 
                \                                        
                 CH2           (CB) the beta-carbon atom 
                /                                        
(CG)           C   CH          (CE3)                     
              //\ /  \\                                   
(CD1)        CH  C    CH       (CD2)  and  (CZ3)         
             |   ||   |                                  
(NE1)        N---CH   CH       (CE2)  and  (CH2)         
            /     \  //                                  
           H       CH          (CZ2)                     

The position of this NE1 donor hydrogen is determined by the positions of the neighbouring atoms CD1 and CE2, since these atoms (together with NE1 itself) define both the plane containing the hydrogen and the direction of the nitrogen-hydrogen bond in that plane. Two pointers are therefore needed, one for CD1 and the other for CE2, and their values are calculated as follows:

The sequence of atoms in a standard Tryptophan Residue is defined in datafile GRUB:

N CA C O CB CG CD1 CD2 NE1 CE2 CE3 CZ2 CZ3 CH2 OXT

and atom CD1 occurs two places before NE1 so that pointer N3IN = -2 while atom CE2 occurs one place after NE1 making N4IN = +1

The following points should be noted:

1. A Type 1 nitrogen cannot accept hydrogen bonds

2. Some tryptophan residues in special locations, or in solutions of unusual pH, might loose the hydrogen from atom NE1 and the values of N1IN etc would then need adjustment. Such changes may be made by editing the GRINKOUT file (See below). Alternatively, another tryptophan residue with a different nitrogen type and different charges and a different ACID name could be added to datafile GRUB.

3. The standard Tryptophan Residue is composed of ATOMS, but an exactly analogous procedure would have been used to find the two pointers if the Type 1 NH nitrogen had been a HETATM.

4. An amide nitrogen NH group also has this geometry. However, protein and peptide backbone NH groups receive special treatment as ATOMS of type -1 as described below.

5. The NH group of guanidine derivatives such as arginine would have this geometry. So would the NH of many aromatic heterocyclics, and the unionised NH group of N-methyl aniline if it was sp² hybridised.

15.1.3. Type -1. (N1IN = -1)

This is a special example of Type 1, and applies exclusively to protein backbone amido nitrogen atoms in mid chain. The geometry is similar to Type 1 above. Note that a Type -1 amido nitrogen is provided in Datafile GRUB for almost every Recognised amino-acid. There are a few exceptions such as proline. Note also that a Type -1 nitrogen cannot accept hydrogen bonds.

15.1.4. Type 2 (N1IN = 2)

This deals with the planar NH2 group at the end of an arginine side chain, or other planar groups of similar geometry. In this case all three pointers N3IN, N4IN and N5IN are required. N3IN identifies the carbon atom (CZ) of arginine to which the NH2 group is directly bonded. N4IN and N5IN define the two heavy atoms bonded to carbon CZ, i.e. the other two nitrogen atoms at the end of the arginine side chain.

The hydrogen atoms bonded to amide nitrogen in the side chains of ASN and GLN are also treated as Type 2. However, in these side chains the terminal NH2 and oxygen groups cannot always be distinguished unequivocally. Special provision is therefore made to deal with this situation. With asparagine, for example, atoms AD1 and AD2 are provided, and these names should be used in the PDB file if the X-ray observations do not adequately distinguish between OD1 and ND2. The use of these names follows the conventions of the Protein Data Bank.

Sometimes it may not be clear if a residue is aspartic acid (ASP) or asparagine (ASN), and the X-ray crystallographer will then use the residue name ASX. Similarly GLX is used if there is confusion between GLU and GLN. The names ASX or GLX are therefore provided in datafile GRUB. An asparagine side-chain Type 2 nitrogen can be the place at which a protein sequence is glycosylated. If this has happened to an asparagine residue, then Programme GRIN will adjust the nitrogen atom and make it Type 1. Message N150 will be sent to GRINLOUT when a glycosylation site is detected, and Message N770 will be sent when the atom type has been changed.

A Type 2 group has sp² character and is flat. It cannot accept hydrogen bonds. Type 32 should be used if the nitrogen has some sp³ character with a tendency to form a lone pair of electrons.

The energy variable JTYPE may take the value 2, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.5. Type -2 (N1IN = -2)

This is also a special case, and deals with the main chain nitrogen of proline which does not bear an hydrogen atom. However, it is essential to give N1IN the value -2 so that the appropriate adjustments can be made if the proline happens to be an N-terminal protein residue (See Type -4 below).

15.1.6. Type 3 (N1IN = 3)

The geometry of a lysine side-chain terminal nitrogen which bears three hydrogens. This has already been described in detail above. A Type 3 NH3 group cannot rotate about the bond which joins the nitrogen to the rest of the molecule. Use Type 83 for a group which can rotate.

The energy variable JTYPE may take the value 3, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.7. Type -3

This deals with the special case of the N-terminal nitrogen of a protein chain, which is treated as a cationic tetrahedral nitrogen bearing three hydrogen atoms. A Type -3 group cannot accept hydrogen bonds. The N-terminal nitrogen of proline or hydroxyproline is Type -4 as described below.

It is never necessary to assign the value N1IN = -3 to such a group in GRUB. It should be assigned Type -1 because it is an amino-acid backbone nitrogen. Programme GRIN will make the necessary adjustments at the N-terminal, and will supply the correct hydrogen atoms for an N-terminal nitrogen in the GRINKOUT file. It does this by calling the Type 3 information as used for a lysine side-chain above. Thus in practice the User should never assign Type -3 to any atom.

15.1.8. Type 4 (N1IN = 4)

The geometry of an hydroxy group in a primary alcohol is Type 4. N3IN identifies the heavy atom to which the oxygen is bonded, and N4IN identifies the preceding atom. Thus the bond vector to the oxygen is known, and eclipsing of the hydrogen by the preceding atom can be avoided. Such an hydroxy group can donate one hydrogen bond and accept two.

The hydrogen position of a Type 4 hydroxyl group is fixed. This allows the User to orient the vector which defines the direction of the donated hydrogen bond, by editing the GRINKOUT file to put the hydrogen exactly where he wishes. This naturally has an effect on the way in which hydrogen bonds are accepted by the hydroxyl group, as well.

Another possibility is to treat the hydroxyl as Type 84, in which rotation of the hydrogen and lone pairs is permitted about the axis joining the oxygen to the rest of the molecule. Moreover Type 34 is provided for phenolic hydroxyl groups, and Type 88 for ionised phenolic hydroxyl.

It sometimes happens that a nominal hydroxyl oxygen atom of the Target has actually reacted to form an ether link with another nearby molecule, or with another atom of its own molecule. For example, this occurs when a straight-chain sugar becomes a furanose or pyranose cyclic sugar, or links to another sugar to form an oligo- or polysaccharide. If the sugars are treated as Recognised Molecules, with their own entries in Datafile GRUB, then Programme GRIN will modify the hydroxyl oxygen ATOM appropriately when this happens. Programme GRIN will turn a Type 4 hydroxyl oxygen ATOM into Type 28 which is the Type of an ether oxygen. Message N780 will be sent to GRINLOUT when when the atom Type has been changed in this way.

The energy variable JTYPE may take the value 4, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.9. Type -4

This deals with the special case of a proline backbone nitrogen at the N-terminal of a protein chain. The nitrogen is treated as a cationic tetrahedral sp³ nitrogen bearing two hydrogen atoms. A Type -4 atom cannot accept hydrogen bonds.

It is never appropriate to assign an atom Type -4. A proline nitrogen should always be assigned Type -2. If it is a proline backbone nitrogen at the N-terminal, then the appropriate adjustments will be made by Programme GRIN automatically. Thus in practice the User should never assign Type -4 to any atom.

Note that Type 22 provides the same geometry for two hydrogens bonded to a tetrahedral sp³ nitrogen HETATM in small molecule mode.

15.1.10. Type 8 (N1IN = 8)

This might be an sp² carbonyl or carboxy oxygen which accepts two hydrogen bonds in the direction of its lone pairs. N3IN points to its nearest bonded neighbour (e.g. the carboxy carbon), and N4IN points to one of the other atoms to which that neighbour is bonded (e.g. the other carboxy oxygen). A Type 8 oxygen cannot donate hydrogen bonds.

Type 8 is also used for other atoms with similar geometry. These include aldehyde, amide, nitro, nitroso, phenolate and sulphonamide, sulphoxide oxygens. In addition it is used for the oxygens of unionised sulphate esters, unionised sulphonate esters, unionised alkyl sulphonates and unionised alkyl sulphinates, as well as sp² nitrogen with two lone pairs and one double bond. On the contrary, Type 64 should be used for phosphate, arsenate, and sulphate or sulphone oxygens.

The energy variable JTYPE may take the value 8, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.11. Type 10 (N1IN = 10)

Type 10 is a reserved number, and may not be used.

15.1.12. Type 11 (N1IN = 11)

Type 11 is a reserved number, and may not be used.

15.1.13. Type 12 (N1IN = 12)

Type 12 is a reserved number, and may not be used.

15.1.14. Type 13 (N1IN = 13)

Type 13 is a reserved number, and may not be used.

15.1.15. Type 14 (N1IN = 14)

Type 14 is a reserved number, and may not be used.

15.1.16. Type 15 (N1IN = 15)

Type 15 is a reserved number, and may not be used.

15.1.17. Type 16 (N1IN = 16)

Type 16 is a reserved number, and may not be used.

15.1.18. Type 17 (N1IN = 17)

Type 17 is a reserved number, and may not be used.

15.1.19. Type 18 (N1IN = 18)

Type 18 is a reserved number, and may not be used.

15.1.20. Type 19 (N1IN = 19)

Type 19 is a reserved number, and may not be used.

15.1.21. Type 20 (N1IN = 20)

This is an sp² atom bonded to two planar hydrogens, such as the CH2 group of 1,1-dimethyl-ethylene. The hydrogens do not make hydrogen bonds, but Type 20 is provided so that all-hydrogen models of small molecules can be generated automatically by Programme GRIN. Note that both the methyl groups of 1,1-dimethyl-ethylene are required in order to define the plane of the Type 20 hydrogens. An error message would be generated for the CH2 group of ethylene or propylene.

15.1.22. Types 21 and 27. (N1IN=21 or 27)

The hydrogen-bonding hydrogens in histidine side chains receive special treatment. The proton is initially assigned to nitrogen ND1 which is Type 21, and nitrogen NE2 is an unprotonated Type 27 nitrogen:

                C           (CA) the alpha-carbon atom 
                 \ 
                  CH2       (CB) 
                 / 
                C           (CG) 
               / \ 
(CD2)         CH  NH        (ND1) Type 21 
              |   | 
(NE2)         N===CH        (CE1) 
Type 27 

The position of the ND1 donor hydrogen is determined by the positions of atoms CG and CE1, since these atoms (together with ND1) define both the plane containing the hydrogen and the direction of the nitrogen-hydrogen bond in that plane. Two pointers are therefore needed, one for CG and the other for CE1.

NE2 is initially treated as an acceptor nitrogen, but the position at which a hydrogen would be bound to this atom is still calculated. Then, when the next Programme GRID encounters a histidine residue with nitrogens of Types 21 and 27, it performs two computations. First, it treats the ring as defined by programme GRIN and datafile GRUB. Then the tautomeric structure is considered in which the nitrogen has migrated from ND1 to NE2, with consequential alterations in the electronic distribution round the ring and the lone pair. After making both computations, Programme GRID decides on the basis of the particular Target/Probe geometry, which is the most appropriate tautomer to use.

TAUTOMERIC HYDROGENS Programme GRIN actually computes both tautomeric positions of the hydrogens bound to nitrogen in the histidine ring in residue HIS. Both are printed to file GRINKOUT, although the next Programme GRID will only use one or the other. Both hydrogen positions are also printed to GRINKOUT for the protonated histidine residue HIP, and neither is printed for HI0.

It should be noted that:

1. On occasion it may not be known which way round the histidine ring is placed, so that atoms ND1 and CD2 would not be identified unequivocally. In this case the atoms NE2 and CE1 would be similarly confused, and the symbols AD1, AD2, AE1 and AE2 are therefore provided in datafile GRUB to deal with the situation. It is necessary to use these atom names in the PDB input file for Programme GRIN. No hydrogen bonding is specified in this case.

2. Some histidine residues in special locations or in solutions of unusual pH might loose the protons from both nitrogen atoms. In these circumstances the residue name should be HI0 (HIzero) which will use Type 97 for both the nitrogen atoms. On the other hand one should use HIP as the residue name if both the nitrogens carry protons at low pH.

3. Note that the same atom names are used for HI0 and HIP as for residue HIS.

4. For the side chain atoms of histidine one may either use ND1 CD1 NE2 CE2 or AD1 AD2 AE1 AE2 as atom names. However, these names should not be mixed in the same histidine molecule.

15.1.23. Type 22 (N1IN = 22)

This is a tetrahedral NH2 group with sp³ geometry, as in the piperidine cation. It has covalent bonds to two adjoining atoms which are marked by the pointers N3IN and N4IN, and it bears two tetrahedrally arranged hydrogen-bonding hydrogen atoms. It cannot accept hydrogen bonds.

The energy variable JTYPE may take the value 22, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

Type -4 provides the same geometry for an N-terminal Proline residue. Type 27 (N1IN = 27)

See Type 21 above for a description of this nitrogen which occurs in the histidine ring.

15.1.24. Type 28 (N1IN = 28)

This is an ether oxygen atom which can accept two weak and poorly oriented hydrogen bonds. It cannot donate.

Note that an ether oxygen atom may sometimes be in a special situation in which it does not have two neighbours at bonding distance. For example, this can happen if a crystal is being studied, and the Target is a cluster of several unit cells. At the edge of the unit cell some oxygens may be left without a neighbour. If this has happened, Programme GRIN will adjust the ether oxygen atom, and will normally make it Type 8 which is a carbonyl oxygen Type. Message N320 or N340 will be sent to GRINLOUT when the atom type has been changed. Note that the electrostatic charge distribution may be disrupted.

The energy variable JTYPE may take the value 28, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

Also see Type 228 below.

15.1.25. Type 30 (N1IN = 30)

This is an sp³ atom bonded to three tetrahedrally arranged hydrogens in a methyl group. The hydrogens do not form hydrogen bonds, but Type 30 is provided so that all-hydrogen models of small molecules can be generated automatically by Programme GRIN.

15.1.26. Type 31 (N1IN = 31)

A tetrahedral sp³ atom which can donate one hydrogen bond, and which is bonded to three other atoms as in cationic trimethylamine: HN(CH3)3+

A Type 31 atom cannot accept hydrogen bonds.

15.1.27. Type 32 (N1IN = 32)

This deals with an NH2 or similar groups. If the two hydrogen positions are not provided in the original PDB file, then Programme GRIN will calculate hydrogen coordinates to give a flat sp² type of NH2 group. This can donate two hydrogen bonds and cannot accept. The hydrogen positions are fixed, and no rotation about the bond from nitrogen to the rest of the molecule is permitted. In this case the NH2 group cannot accept a hydrogen bond, and the Type 32 group resembles a Type 2 as described above.

If reasonable hydrogen coordinates are provided in the PDB file, they will be accepted. As before the hydrogen positions are fixed, and the group can donate two hydrogen bonds. If the nitrogen is pyramidal with sp³ geometry and bond angles of about 109 degrees, then an sp³ lone pair is assumed and can accept a hydrogen bond. On the other hand there is no lone pair if the nitrogen is flat with 120 degree bond angles and sp² geometry. When the nitrogen has intermediate bond angles between 109 and 120 degrees, the presence of a partial lone pair is assumed. No rotation is permitted around the bond from nitrogen to the rest of the Target molecule, so the hydrogen bond orientations are fixed.

A Type 32 nitrogen resembles a Type 82 group when the given hydrogen coordinates define sp³ geometry, with one important difference. The Type 82 group can rotate about the bond joining the nitrogen to the rest of the molecule, but no rotation is allowed for Type 32.

The energy variable JTYPE may not take the value 32. You should use Type 2 or Type 82 (or both) for a Probe with this Type of hydrogen-bond geometry.

15.1.28. Type 34 (N1IN = 34)

This might be an aromatic sp² hydroxyl group as found in phenol or the amino-acid tyrosine. N3IN and N4IN have the same meanings as in Type 4 above, but they produce a different hydrogen geometry. A Type 34 hydrogen-bonding hydrogen atom is in the plane of the aromatic ring, and the Type 34 oxygen can donate one and accept one hydrogen bond. These hydrogen bonds are both constrained to be near the plane of the ring, and both the alternative positions of the hydrogen are tested. When the hydrogen is to the right, the lone pair of the oxygen is to the left, and vice versa.

Type 34 is also used for similar groups, such as an sp² imine nitrogen having one hydrogen atom and one lone pair, or the sp² OH group of an unionised carboxylic acid.

The energy variable JTYPE may take the value 34, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.29. Type 35 (N1IN = 35)

This Type is only used with ATOMS and not with HETATMS. It is a methylene group of the Target molecule to which an amine nitrogen (Type 82 or 83) or a hydroxyl oxygen (Type 84) is bonded. It is therefore bonded both to the hydrogen-bonding atom (ie: the nitrogen or oxygen), and to another heavy atom which we will call H1:

                          H1  <==  The adjacent Heavy atom 
                           \ 
The Type 35 Methylene ==>   CH2----O   <==  The hydroxyl oxygen
                              \ 
    The hydroxyl hydrogen ==>  H

The torsion angle: H1 - CH2 - O - H has little effect on the hydrogen-bonding strength of the oxygen when that oxygen is providing the lone pair electrons which accept the hydrogen. On the other hand there is evidence (Liljefors, 1996, Personal Communication) showing that the torsion angle does have a detectable influence when the hydrogen comes from the hydroxyl group of the Target, and is donated from the hydroxyl to a lone pair of the Probe.

This influence is now taken into account by the energy functions of Programme Grid, but Grid must know how many heavy atoms and how many hydrogens are bonded to the sp³ carbon atom. Type 35 is therefore a flag which indicates that only one heavy atom influences the torsion, as shown above. Types 36 and 37 are used when more heavy atoms have an influence (see below).

The effect of the new energy functions is to discourage the donation of a hydrogen bond by sp³ hydroxyl and amine groups, and this sometimes causes the bonding pattern to alter. Many Probes simply turn round and donate to the hydroxyl, when they might have accepted according to the energy functions in earlier Versions of the Programmes. When this happens the overall effect on the predicted binding energy is small, but of course the binding geometry is changed.

The most significant influence of the new energy functions is when the Probe can accept a hydrogen from the Target hydroxyl, but cannot donate. With a carbonyl oxygen Probe, for example, the most unfavourable H1 - CH2 - O - H torsion angle can diminish the predicted hydrogen-bonding energy by more than 1 Kcal/mole. This is in accord with Professor Liljefors findings, but such a large effect is not often observed in practice.

15.1.30. Type 36 (N1IN = 36)

This Type is analogous to Type 35 above, and is only used with ATOMS but not HETATMS. It is a CH group of the Target molecule to which an amine nitrogen (Type 82 or 83) or a hydroxyl oxygen (Type 84) is bonded. It is therefore bonded both to the hydrogen-bonding atom (i.e.: the nitrogen or oxygen), and to two other heavy atoms which we will call H1 and H2:

                         H1   H2  <==  The adjacent Heavy atoms 
                           \ / 
 The Type 36 CH group ==>   CH-----O   <==  The hydroxyl oxygen 
                            | 
The hydroxyl hydrogen ==>   H

The torsion angle is treated as described for Type 35 above, but its detailed influence is modulated because there are two heavy atoms H1 and H2 bonded to the carbon.

Type 36 is therefore a flag which indicates that two heavy atoms influence the torsion angle, and the strength of the hydrogen bonds made by the hydroxyl oxygen or amine nitrogen atoms, as shown above.

15.1.31. Type 37 (N1IN = 37)

This Type is analogous to Type 35 above, and is only used with ATOMS but not HETATMS. It is a carbon atom of the Target molecule to which an amine nitrogen (Type 82 or 83) or a hydroxyl oxygen (Type 84) is bonded. this carbon is bonded both to the hydrogen-bonding atom (ie: the nitrogen or oxygen), and to three other heavy atoms which we will call H1, H2 and H3:

                              H3 
                           H1 | H2  <== The adjacent Heavy atoms 
                             \|/  
The Type 37 carbon atom ==>   CH-----O  <==  The hydroxyl oxygen 
                              | 
The hydroxyl hydrogen ==>     H 

The torsion angle is treated as described for Type 35 above, but its detailed influence is modulated because there are three heavy atoms H1, H2 and H3 bonded to the carbon.

Type 37 is therefore a flag which indicates that three heavy atoms influence the torsion angle and the strength of the hydrogen bonds made by the hydroxyl oxygen or amine nitrogen atoms, as shown above.

15.1.32. Type 40 (N1IN = 40)

This might be a planar sp² atom bonded to one hydrogen, such as an sp² carbon in a benzene ring or the central carbon of propylene. The hydrogens do not form hydrogen bonds, but Type 40 is provided so that all-hydrogen models of small molecules can be generated automatically by Programme GRIN.

Type 40 is also used for the hydrogen of an aldehyde, or a formate anion, or for the hydrogen bonded to the carbon of formic acid.

15.1.33. Type 44 (N1IN = 44)

This might be an aromatic sp² hydroxyl group as found in phenol or neutral (unionised) acetic acid. N3IN and N4IN have the same meanings as in Type 4 or Type 34 above, but they produce different effects because a Type 44 oxygen can donate one and accept one hydrogen bond with fixed orientations.

With a Type 44 atom the hydrogen-bonding hydrogen atom will tend to be in the plane of the aromatic ring, but the positions of the hydrogen and the lone pair cannot exchange. Type 44 differs in this way from Type 34 above, in which both the alternative positions of the hydrogen and lone pair are tested. However with this Type 44, when the hydrogen is to the right it is fixed there, and the lone pair of the oxygen is then fixed to the left. These positions are not swapped over automatically with Type 44, but are determined by the coordinates of the hydrogen which can be chosen by the User.

Type 44 may also be used for similar groups, such as an sp² imine nitrogen having one hydrogen atom and one lone pair.

The energy variable JTYPE should not take the value 44. Use Type 34 if the Probe is to be assigned this Type of hydrogen-bond geometry.

15.1.34. Type 50 (N1IN = 50)

This is an aliphatic tetrahedral sp³ atom bonded to two hydrogens, such as an sp³ carbon in a -CH2- methylene group. The hydrogens do not form hydrogen bonds, but Type 50 is provided so that all-hydrogen models of small molecules can be generated automatically by Programme GRIN.

15.1.35. Type 51 (N1IN = 51)

This is a pyramidal atom bonded to one hydrogen and two other atoms. If the bond angles are more or less tetrahedral sp³ (i.e. approximately 109 degrees) it will also carry a lone pair as in the unionised di-methylamine molecule :NH(CH3)2 If the angles are larger, so that the group is flatter with more sp² character as in an aromatic heterocycle, then the lone pair will be weakened or absent.

Two tautomeric arrangements are considered, because the positions of the hydrogen and the lone pair can exchange in a Type 51 atom. You should use Type 61 if you wish to fix the hydrogen of the Target in one position, and prevent tautomerism. The energy variable JTYPE may take the value 51, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.36. Type 60 (N1IN = 60)

This might be an sp³ sulphydryl sulphur, or atom with similar geometry. It carries one hydrogen, but can neither donate nor accept hydrogen bonds. Type 60 might also be used to describe an aliphatic hydroxyl group, for example, if the User wished to exclude the possibility of that particular hydroxyl from making hydrogen bonds.

15.1.37. Type 61 (N1IN = 61)

This is a pyramidal atom like Type 51 above. It is bonded to one hydrogen and two other atoms of the Target. If the bond angles are more or less tetrahedral sp³ (i.e. approximately 109 degrees) it will also carry a lone pair as in the unionised di-methylamine molecule :NH(CH3)2 If the angles are larger, so that the group is flatter with more sp² character as in aromatic heterocycles, then the lone pair will be weakened or absent.

The tautomeric arrangement is fixed, and the positions of the hydrogen and the lone pair do not exchange in a Type 61 atom. You should use Type 51 if you want to consider both tautomeric forms of the Target.

A Probe can always rotate, and swop the positions of its hydrogen and its lone pair in order to interact more favourably with the Target. This Type of atom in a Probe must therefore have the value JTYPE=51. The value TYPE=61 may only be used in order to describe an atom or hetatm of the Target.

15.1.38. Type 64 (N1IN = 64)

This might be an oxygen atom bonded to phosphorus in a phosphate group. The oxygen is not bonded to any other atom, and does not donate hydrogen bonds. It can accept two hydrogen bonds from a circular locus, as if free rotation of two lone pairs could occur round the P-O axis at the tetra- hedral angle. The hydrogen bond vector is therefore not fixed but can sweep through an arc, and in this way can generate a halo of GRID contours defining an annulus of favourable hydrogen-bonding interactions. The lone pairs of a Type 84 atom produce a similar effect.

Type 64 should also be used for oxygen bonded only to the central heavy atom of arsenate group.

Type 64 should NOT be used if the oxygen is covalently bonded to a hydrogen atom, as well as to the central heavy atom of the group. It should NOT be used for the linking oxygen between two phosphorus atoms in poly-phosphates. It should NOT be used for carbonyl, carboxy or aldehyde oxygens.

Note that atom O3P of the 5-phosphate group in DNA or RNA is defined as type 64. However, this atom is only present if the group occurs at the 5* terminus of the chain. The linking atom in mid-chain is O3*.

15.1.39. Type 70 (N1IN = 70)

This is a linear acetylenic sp atom bonded to one hydrogen, such as an sp carbon in an acetylene group. The hydrogens do not form hydrogen bonds, but Type 70 is provided so that all-hydrogen models of small molecules can be generated automatically by Programme GRIN.

15.1.40. Type 71 (N1IN = 71)

This is a linear acetylenic sp atom bonded to one hydrogen, such as an sp carbon in an acetylene group. A Type 71 atom cannot accept hydrogen bonds, but in contrast to Type 70 above it can donate one hydrogen bond.

15.1.41. Type 74 (N1IN = 74)

This is a fluorine atom in all its covalently-bound forms. The atom accepts upto two hydrogen bonds, is flat sp² type with its two lone pairs free of rotating about the C-F axis. The resulting field has a circular shape: circular minima are located at 120 degrees as for the Type 64.

Peculiarity of Type 74 is the lower directionality of hydrogen-bonding, typical of fluorine atoms. This feature allows the field (generated with a classic donor probe, such as N1) of organic fluorines to be consistent with experimental hydrogen-bonding interactions found on the PDB.

At the same time di-fluoro and tri-fluoro groups have particular shape when the Type 74 is involved in hydrogen-bonding: the higher contribute from hydrogen-bonding is in the region between two or three fluorine atoms.

15.1.42. Type 80 (N1IN = 80)

This is a tetrahedral aliphatic sp³ atom bonded to one hydrogen and three non-hydrogen atoms, such as the CH extended atom of HC(CH3)3. The hydrogen of the CH group does not form hydrogen bonds, but Type 80 is provided so that all-hydrogen models of small molecules can be generated automatically by Programme GRIN.

15.1.43. Type 82 (N1IN = 82)

This is a tetrahedral sp³ atom bonded to two hydrogens. It also carries one lone pair and is bonded to one other atom, as in the unionised :NH2.CH2.CH3 ethylamine molecule. Like the hydroxyl Type 84 below, a Type 82 atom can rotate about the axis joining the nitrogen to the rest of the molecule. The hydrogen bond vector is therefore not fixed but can sweep through an arc, and in this way can generate a halo of GRID contours defining an annulus of favourable hydrogen-bonding interactions. The lone pairs of a type 82 atom produce a similar effect.

If the hydrogen coordinates are given in the original PDB file, and they define bond angles greater than 109 degrees, then the group may have some sp² character. In this case you should consider using Type 32 as defined above.

The energy variable JTYPE may take the value 82, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

Also see Type 282 below

15.1.44. Type 83 (N1IN = 83)

This is a tetrahedral sp³ cationic amino nitrogen atom bonded to three hydrogens, like the Type 3 lysine amino group described in detail above. Unlike the Type 3, however, a Type 83 amino can rotate about the axis joining the nitrogen to the rest of the molecule. The hydrogen bond vectors are therefore not fixed but can sweep through an arc, as they can in Type 82 above, and in this way they generate a halo of GRID contours defining an annulus of favourable hydrogen-bonding interactions.

The energy variable JTYPE may take the value 83, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

Also see Type 283 below.

15.1.45. Type 84 (N1IN = 84)

This is a tetrahedral sp³ hydroxyl oxygen atom bonded to one hydrogen, like the Type 4 hydroxyl group described in detail above. Unlike the Type 4, however, a Type 84 hydroxyl can rotate about the axis joining the oxygen to the rest of the molecule. The hydrogen bond vector is therefore not fixed but can sweep through an arc, and in this way can generate a halo of GRID contours defining an annulus of favourable hydrogen-bonding interactions.

The Type 84 hydroxyl group also bears two lone pairs. These sweep through an arc at the same time as the hydroxyl hydrogen, and also generate a halo of favourable interactions for Probe groups which can donate a hydrogen bond to the hydroxyl group.

An hydroxyl oxygen atom may have reacted to form an ether link. For example, this occurs when a straight-chain sugar molecule becomes a furanose or pyranose cyclic sugar, or links to another sugar to form an oligo- or polysaccharide. If this has happened Programme GRIN will adjust the hydroxyl oxygen atom, and make it Type 28 which is the Type of an ether oxygen. Message N780 will be sent to GRINLOUT when when the atom type is changed.

The energy variable JTYPE may take the value 84, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

Also see Type 284 below

15.1.46. Type 88 (N1IN = 88)

This is the oxygen of a phenol which is ionised. It therefore is not bonded to hydrogen, but bears a partial negative charge and two lone pairs. The bond from the oxygen to the aromatic ring has some double bond character, and the lone pairs are therefore constrained to stay in the plane of the ring. No hydrogen bonds are donated, but one or two may be accepted by a Type 88 atom.

Another possibility is to treat the group as an unionised phenolic hydroxyl which is Type 34.

The energy variable JTYPE may take the value 88, which indicates that the Probe may be assigned this Type of hydrogen-bond geometry.

15.1.47. Type 91 (N1IN = 91)

Type 91 is exclusively used for the hydrophobic Probe, which finds places at which hydrophobic atoms on the surface of a Target molecule will make favourable interactions with hydrophobic atoms on another molecule. It is a distinguishing characteristic of these hydrophobic interactions that they only occur when both the molecules are immersed in water.

This hydrophobic Probe may be regarded as a modified water Probe. Like water, it must be able donate and accept hydrogen bonds, and must be electrically neutral.