Identi fication of Pockets on Protein Surface to Predict Protein–Ligand Binding Sites - Identification of Ligand Binding Site and Protein-Protein Interaction Area - page 31

D MIN <= Cutoff
Protein
Potential ligand-binding residues
Fig. 2.4 The illustration of residue mapping step in metaPocket. The smaller spheres indicate
the pocket sites from single methods and the bigger sphere indicates the meta-pocket site of
metaPocket. The regions surrounded by thin dotted lines out of protein are the original clusters
of each single method. The region surrounded by the thicker solid line is the cluster of the
meta-pocket generated by metaPocket after merging all the clusters of single methods. The dotted
line in the protein indicates the potential ligand-binding residues within a certain distance
(threshold: D MIN ) to the cluster of meta-pocket sites
hierarchical clustering approach (single-linkage clustering) to cluster these 24 single
pocket sites according to their spatial similarity. The distance cut-off threshold is set
to 8 Å here. That is, two single pocket sites will be clustered into one meta-pocket site
if they are within 8 Å. After clustering, the total z-score for each cluster is calculated
and serve as the final scoring function to re-rank the final meta-pocket sites. In the
end, the mass center for each final cluster is calculated and is represented as the final
meta-pocket site in the output of MetaPocket.
Mapping ligand-binding residues around the pocket site . The purpose of this
step is to identify the functional residues around the identified meta-pocket site
which could be the potential ligand binding sites on protein surface. As illustrated
in Fig. 2.4 , metaPocket uses a synthetically way to identify those residues which
might contribute to protein-ligand interaction. As we mentioned above, each method
outputs a cluster of probe points for each pocket site. In this step, the probe points
from each single method are merged in the same meta-pocket site. Then a big cluster
of probe points is obtained for each meta-pocket site. Those surface residues, whose
any atoms are within a certain distance (5 Å used here) to the probe points in the