2025 Denovo tutorial 2 with PDBID 1XMU

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). Open chimera and select the atoms to delete. Save the mol2 file

DOCK6 input

=