2024 Denovo tutorial 3 with PDBID 1Y0X

Introduction

Continuing from Virtual Screening tutorial, we have the De Novo design tutorial. De Novo means from the beginning, thus, in this tutorial, we are learning to design the molecule that can bind to our protein from scratch. There are 3 different algorithms for the De Novo Design:

1. Generic DeNovo Design
2. Focused Fragment Design
3. DeNovo Refinement

Setting Up Your Environment

Creating new directories in your workspace like the similar:

De Novo Refinement

This algorithm allows us to refine an existing molecule by deleting part of the molecule and let DOCK6 decide what chemical group can be regrow from the deleted area to fit with the protein pocket. Hear is how you can perform it:

Set up your dummy atom

1. Open the protein and ligand in chimera
2. Choose a chemical group inside the binding pocket that you want to delete
3. Get the name of the first atom connecting the chemical group to the rest of the compound by placing the mouse on top of the structure
4. Delete all other atoms after that first atom that you located
5. Save the .mol2 file of the ligand and open it in a text editor program
6. Change the name of the Atom to "DU1" and the atom type to "Du"
7. Save the .mol2 file again

Running De Novo Refinement

Locate to 012 directory and scp the .mol2 file into the directory. Make an input file for DOCK with the following input: