In particular, the combination of MD simulations and pose clustering to guide site-directed mutagenesis has resulted in the design of enzyme variants that exhibit altered functional properties, such as homotropic cooperativity, substrate inhibition, and substrate affinities, in vitro.
If a substantial number of low energy docked poses cluster in a narrow vicinity of the native structure of the dimer, then one can assume that there is a well-defined free energy well around the native state, which makes the interaction stable.
The hDHFR ligands in cluster c had hydrogen bonds (E30-OE1, E30-OE2, V115-0, in-0 in green dotted lines) and van der Waals forces shown by a blue arc (I60-CAR, F31-RING) revealing that binding interactions of each docked pose within cluster c were similar.
Binding affinities were calculated from this 200-pose cluster using a ChemScore Fitness function.
Such figures emphasize the danger posed by cluster submunitions, which, because of their higher explosive yield, are more likely than land mines to result in one or more fatalities upon accidental detonation.
After organizations such as the International Campaign to Ban Landmines successfully lobbied for the adoption of the Mine Ban Treaty in 1997, human rights groups sought to address the similar danger posed by cluster munitions.
UNICEF is supporting a public information campaign, incorporating television and radio advertisements, together with posters and leaflets, warning people about the danger posed by cluster bombs and other lethal munitions.
The PatchDock algorithm is inspired by object recognition and an image segmentation technique used in computer vision and applies geometric hashing and pose-clustering matching to match convex and concave patches of interacting surfaces [ 79].
One of the puzzles posed by clusters is the question of how properties of small clusters evolve with size into properties of bulk matter.
Thus, only the best scoring pose within each cluster would be used for free energy calculations.
Results from the repeated-measure ANOVA omnibus tests indicated a significant main effect of pose within each cluster of top ranked 4 5 poses for all joints, planes of motion, and directions (p = 0.00 – 0.00).
