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MOLECULAR DOCKING

Presented by

Aamna Parveen

Assistant Professor

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Agenda

INTRODUCTION

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IMPORTANCE OF DOCKING

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TYPES

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KEY STAGES IN DOCKING

APPLICATIONS

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Introduction

In the field of molecular modelling, docking is a method which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex.

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Knowledge of the preferred orientation in turn may be used to predict the strength of association or binding affinity between two molecules using for scoring functions.

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It is a computational procedure to find out the active ligand which can bind with target site effectively. The molecular docking studies are useful to find out the lead compound which can fit into receptor effectively. The docking studies give reliable information about the perfect orientation of ligand with protein and to use same in rational drug design.

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Importance of Molecular Docking

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Prediction of the binding affinity (Scoring Function)

Identification of ligand’s correct binding geometry in the binding site.

Rational Design of Drug

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Types of Docking

  • In rigid docking, the internal geometry of the receptor and ligand are treated as rigid.

Rigid Docking ( Lock And Key)

Flexible Docking ( Induced Fit)

  • An enumeration on the rotations of one of the molecules (usually smaller one) is performed. Every rotation the energy is calculated. Later the most optimum pose is selected.

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Docking can be between

  • Protein-Ligand
  • Protein-Protein
  • Protein- Nucleotide

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Key Stages In Docking

Target/Receptor Selection And Preparation

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Ligand Selection And Preparation

Docking

Evaluating Docking Results

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Receptor Selection And Preparation

  • BUILDING THE RECEPTOR

The 3D structure of the receptor should be considered which can be download from PDB.

The available structure should be processed.

The receptor should be biologically active and stable.

  • IDENTIFICATION OF THE ACTIVE SITE

The active site within the receptor should be identified.

The receptor may have many active sites but the one of the interest should be selected.

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Ligand Selection And Preparation

  • Ligand can be obtained from various databases like ZINC, PubChem or can be selected using tools like Chem-sketch.

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Docking

  • The ligand is docked onto the receptor and the interactions are checked. The Scoring function generates score, depending on which the best fit ligand is selected.

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Software

  • SANJEEVINI
  • AUTODOCK
  • GEMDOCK
  • HEX PROTEIN DOCKING

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Applications

  • Virtual Screening (Hit identification)

Docking with a scoring function can be used to quickly screen large databases of potential drugs in silico to identify molecules that are likely to bind to protein target of interest.

  • Drug discovery (lead optimization)

Docking can be used to predict in where and in which relative orientation a ligand binds to a protein. This information may in turn be used to design more potent and selective analogues.

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Thank you