2018 DOCK tutorial 2 with PDBID 1C87
For additional Rizzo Lab tutorials see DOCK Tutorials. Use this link Wiki Formatting as a reference for editing the wiki. This tutorial was developed collaboratively by the AMS 536 class of 2018, using DOCK v6.8 and it shows how to dock a ligand into a receptor.
I. Introduction
DOCK
DOCK is a molecular docking program used in drug discovery. It was developed by Irwin D. Kuntz, Jr. and colleagues at UCSF (see UCSF DOCK). This program, given a protein binding site and a small molecule, tries to predict the correct binding mode of the small molecule in the binding site, and the associated binding energy. Small molecules with highly favorable binding energies could be new drug leads. This makes DOCK a valuable drug discovery tool. DOCK is typically used to screen massive libraries of millions of compounds against a protein to isolate potential drug leads. These leads are then further studied, and could eventually result in a new, marketable drug. DOCK works well as a screening procedure for generating leads, but is not currently as useful for optimization of those leads.
DOCK 6 uses an incremental construction algorithm called anchor and grow. It is described by a three-step process:
- Rigid portion of ligand (anchor) is docked by geometric methods.
- Non-rigid segments added in layers; energy minimized.
- The resulting configurations are 'pruned' and energy re-minimized, yielding the docked configurations.
1C87
In this tutorial we will use PDB code 1C87, which is the crystal structure of protein tyrosine phosphatase 1B complexed with 2-(oxalyl-amino-4,7-dihydro-5H-thieno[2,3-C]pyran-3-carboxylic acid.
