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dMIFs
The dMIFs for each feature type can be saved as contour maps in different formats (xplor, cns, kont). LigandScout can read kont-files, MOE and PyMol prefer cns or xplor. The scores do not represent any thermodynamic energy but are defined as follows:
These maps describe the occupancy of the binding pocket by water molecules. A score of 20 means, that in 20 % of the frames there is a water molecule at this position. Water molecules involved in more than 2 hydrogen bonds are not included in the shape dMIF.
h2o - general shape dMIF without any hydrogen bond criteria
shape - same as h2o except that only water molecules are included that are involved in not more than 2 hydrogen bonds, since replacing a water with more than two hydrogen bonds might be energetically unfavorable, this dMIF is used for exclusion volume placement
Hydrogen bonding features are separated into different types. A score of 20 means, that in 20 % of the frame there is a water molecule involved in the distinct hydrogen bonding interaction type at this position.
hb - water molecule is involved in not more than 2 hydrogen bonds
hd_combo - water molecules at this position are involved in one or two hydrogen bonds as donor
hd - water molecules at this position are involved in exactly one hydrogen bond as donor
hd2 - water molecules at this position are involved in exactly two hydrogen bonds as donor
ha_combo - water molecules at this position are involved in one or two hydrogen bonds as acceptor
ha - water molecules at this position are involved in exactly one hydrogen bond as acceptor
ha2 - water molecules at this position are involved in exactly two hydrogen bonds as acceptor
hda - water molecules at this position are involved in exactly two hydrogen bonds once as donor, once as acceptor
tw - trapped water molecules at this position are involved in more than 2 hydrogen bonds, replacing a water with more than two hydrogen bonds might be energetically unfavorable, maybe interesting as bridging water molecule in later lead optimization
Grid points are scored individually based on angle and distance to aromatic and positively charged atom groups. A score of 10 means, that in 10 % of the frames there is an atom group within the optimal distance fulfilling the angle criteria for aromatic interactions.
ai - water molecules at this position are close to aromatic or positively charged atom groups, grid points close to such water molecules are evaluated separately for pi-stacking, t-stacking and cation-pi interactions
Ionizable interactions are scored based on the distance between water and ionizable as well as aromatic atom groups. Additionally, pi and ni quench each other. A score of 10 means, that in 10 % of the frames there is an atom group within the optimal distance for ionizable interaction.
pi - water molecules at this position are in close proximity to a negatively charged or aromatic atom group
ni - water molecules at this position are in close proximity to a positively charged atom group
Hydrophobicity is estimated by counting hydrophobic atoms within 5 A around the water molecules. Additionally, the rough atom count is scaled by buriedness to favor enclosed water molecules.
hi - water molecules at this position are in a hydrophobic environment, number of hydrophobic atoms in the environment are determined, sclaed by buriedness and added to hi score in each frame, water molecules need to be more than 4 A away from charged centers to be considered for this score
hi_norm - describes the average number of hydrophobic atoms within 5 A scaled by buriedness, only calculated for grid points with a shape score equal or higher than 1, a score of 5.3 means, that whenever a water molecule is at this position, on average 5.3 hydrophobic atoms (scaled by buriedness) were within 5 A