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Pocketome Screening

Pocketome Screening

Pocketome is a collection of liganded “pockets” created from crystal structures of proteins in complex with their ligands.  Each pocket is constructed from a set of 3D grid-based force field potentials representing both a small molecule ligand or short peptide and its protein environment.

The pocketome screening is performed first by minimizing a ligand, and then docking it into a grid force field potential in internal coordinates space.

The Q-MOL kinase pocketome consists of over 1500 pockets containing redundant set of kinases regardless of species and type of binding site.

 

Understanding Binding Probability

 

The Q-MOL pocket docking protocol computes binding probability according to degree of satisfying structural constrains of a binding pocket by ligand fetaures.  It is important to understand the difference between binding probability and actual affinity to the target.

Consider the figure above.  It is a schematic representation of 3 ligands docked into a pocket.  The predicted binding probability is the SAME across the ligands: A = B = C.  In all three cases, all ligand-related structural constrains are satisfied. 

However, the actual binding affinity is changing in the following way: A < B < C.  In reality, this translates into a case when affinity of ligand C is in nanomolar range, while the affinity of its substructure (fragment) A is in high micromolar or even milimolar range.  In spite of its low affinity, ligand A could still be highly specific because of unique features of corresponding pocket.

Because of nature of Q-MOL grid potentials and docking methodology, the predicted binding probability does not differentiate between inhibitors or activators.