Revision as of 16:50, 2 March 2023

Introduction

This next section will walk you through the three options for DeNovo Design:

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

and will be a continuation of the Virtual Screening tutorial. We will continue this work with #4s0v from the Protein Data Base.

Setting Up Your Environment

For this section we will need to create some more directories following this structure:

DeNovo Refinement

The DeNovo Refinement calculation/algorithm within DOCK is an interesting way to determine the effects on a ligand/protein interaction by changing part of the small molecule. For this tutorial we are going to change just a terminal ring on our ligand and see what different residues DOCK suggests we look into further.

The overall idea behind this refinement is to delete a portion of your ligand, replace the "stub" atom (or "anchor" atom) which is now not bonded to anything with a dummy atom, and ask DOCK to find an alternative.

1. Step 1: Open the ligand minimized mol2 file we generated in the previous tutorial into Chimera.
2. Step 2: Open the protein into the same session
3. Step 3: Examine the binding site and choose a residue on the ligand that's pointing towards the inside of the binding site. For our protein this detailed section looks like:

Generic DeNovo Design

Focused Fragment Design