2025 Denovo tutorial 2 with PDBID 1XMU
Contents
Introduction
This tutorial describes de novo method to refine ligand structure(s) using DOCK6. Rather than screening existing compounds, de novo refinement adds fragments based on known bioactive compounds, aiming to produce new ligands that bind more tightly to protein receptors than current options. This strategy is particularly valuable for:
- Improving suboptimal ligand binding profiles
- Overcoming resistance mechanisms
- Exploring novel scaffolds while maintaining critical pharmacophore features
In this tutorial, we will utilize PDB structure 1XMU - Catalytic Domain Of Human Phosphodiesterase 4B In Complex With Roflumilast.
System Preparation
We first prepare a folder to contain all the input and output files for de novo refinement for 1XMU. This is the current directory structure under the upper directory dock6-1xmu.
Input File
Modify Ligand with Dummy Atom
Below shows the original ligand with hydrogen (mol2 file).
Select the atoms to delete and save the mol2 file as 1xmu_lig_wDu.mol2. Hover the cursor over the atom that you intend to change to a dummy atom. Here we are changing the C21 to a dummy atom.
Open the 1xmu_lig_wDu.mol2 file and edit the C21 atom type to Du as shown below.
Next reopen the 1xmu_lig_wDu.mol2 file to observe if the corresponding atom is now represented as Du in magenta.
DOCK6 input
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