Practical Chemoinformatics

pp 271-316


Active Site-Directed Pose Prediction Programs for Efficient Filtering of Molecules

  • Muthukumarasamy KarthikeyanAffiliated withDigital Information Resource Centre, National Chemical Laboratory Email author 
  • , Renu VyasAffiliated withScientist (DST) Division of Chemical Engineering and Process Development, National Chemical Laboratory

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It is well known that the three-dimensional structure of a protein is a prerequisite in the field of structure-based drug discovery. Proteins are usually crystallized along with substrates (small molecules) and the site of binding is used for further computational study and virtual screening. Homology is a method that helps in modelling when a protein structure lacks co-crystallized ligands and requires knowledge of the binding site or the sequences which are yet to be crystallized, that require some structural understanding to correlate with biological functions. Homology modelling and active site prediction steps are discussed in detail using standard state-of-the-art software. Knowing the exact sites on a particular protein structure where other molecules can bind and interact is of paramount importance for any drug design effort. Having learnt the basic elements of docking, in this chapter we probe further into the binding sites and the specific properties that impart them the capability of getting bound by ligands. Active site-based features like topology, shape volume and amino acid composition all contribute to its preference for binding to a particular ligand molecule. Deducing this knowledge is the crux of an efficient active site-based screening of molecules. Active site information also helps in building a receptor-based pharmacophore query which can be applied as a constraint while screening molecular libraries. The later section therefore highlights some efforts towards active site-based virtual screening of molecules using an internally developed program which computes phi–psi-based fingerprints of proteins and binary fingerprints of ligands as a pre-filtering step for docking.


Active site Homology modelling Phi–psi fingerprints Drug design