Hydrogen bonds are frequently important in ligand binding. These interactions can be modeled explicitly in AutoDock .
In order to save having two types of hydrogen grid maps, and thus conserve disk space, we normally use ligands with just one type of hydrogen, namely polar hydrogens. Polar hydrogens can be defined here as those bonded to heteroatoms like nitrogen and oxygen, while non-polar hydrogens are bonded to carbon atoms.
If you want to model non-polar hydrogens as well, you would need a separate map for such hydrogens. You could use the atom type code `h' for non-polar hydrogens, and `H' for polar hydrogens. Use 12-6 to distinguish non-polar hygrogens, and 12-10 for polar hydrogens.
The user must specify the appropriate 12-10 parameters in the AutoGrid parameter file, and on the correct lines. Pairwise atomic interaction energy parameters are always given in blocks of 7 lines, in the order: C, N, O, S, H, X, M. X and M are "spare" atom types: If there were phosphorus atoms in the receptor, X could be used as P. For example, to model donor hydrogens in the ligand, 12-10 parameters would be needed in the hydrogen parameter block, but only for H-bond acceptors, N,O and S (second, third and fourth lines in the H-parameters). The other parameters remain as 12-6 Lennard-Jones values (C,H,X and M). In order to keep the symmetry of pairwise energetics (H-O is the same as O-H), the user must specify 12-10 parameters for H (fifth line) in the N, O and S-parameter blocks.
Atoms i-j |
reqm,ij----------/ Å |
eij/ kcal mol-1 |
C12/ kcal mol-1Å12 |
C10/ kcal mol-1Å6 |
|---|---|---|---|---|
AutoGrid detects hydrogen bond parameters in the grid parameter file, if either n is not 12 or m is not 6. If so, the pairwise interaction is modulated by a function of the cosine of the hydrogen bond angle. This takes into account the directionality of hydrogen-bonds.
AutoGrid incorporates the angular dependence of the hydrogen bond potential. The ideal hydrogen bond would have an angle, q, of 180° between the lone-pair of the acceptor atom, the polar hydrogen and the donor atom, thus:
As q decreases, the strength of the hydrogen bond diminishes. There are no hydrogen bonds when q is 90° or less.
Note : If you use hydrogen bonding for nitrogen, you may need to distinguish between nitrogens that can be acceptors and those that can be donors. The above settings for N and H would allow >NH to accept a hydrogen bond. To avoid this, such nitrogens should be treated as 12-6 non-hydrogen bonders: used `n' as the atom type code instead of `N'. This would mean, of course, an extra grid map.
If you use polar and non-polar hydrogens, for example, with atom type codes of `H' and `h', you must edit the atom names in the PDBQ files by hand. This would apply to different flavours of nitrogen, `N' for polar and `n' for non-polar; or carbon, `C' for aliphatic carbons and `A' for aromatic carbons.