Revision as of 13:31, 13 February 2020

This tutorial is created by AMS 536 Spring 2020 Group 4. Group 4 members include Steven Pak, Caitlyn Cardetti, MiaoMiao He and Chuanzhou (Joey) Hu.

How to for selecting protein: Pick a protein with few substrates and rotational bonds?

The PDB code chosen is 6UZW which is for the crystal structure of GLUN1/GLUN2A ligand-binding domain in complex with glycine and UBP791.

Dock Prep Program used: Chimera

I. Introduction

DOCK

DOCK 6.9 is a molecular modeling program that identifies interactions between chemical compounds and the receptors. DOCK has many features that can help with drug discovery( ex: Virtual Screening and Denovo). This tutorial will show us how to use Virtual Screening.

6UZW

The tutorial will be based on the PDB file 6UZE downloaded from the PDB Database. 6UZW is the crystal structure for GLUN1/GLUN2A complexed with (2S,3R)-1-[7-(2-carboxyethyl)phenanthrene-2-carbonyl]piperazine-2,3-dicarboxylic acid and glycine.

Step 1. Separate protein and ligand

Step 2. Delete H2O molecules in Chimera to reduce computing time.

• To delete: Select > Residues > H O H - they should be highlighted Click Actions > Atoms/Bonds > delete H2O molecules should now be deleted.

Step 3. Add H's.

• PDB codes do not contain H's due to low electron density.
• To add H's Tools > Structure Editing > AddH
• H's MUST be added before you add charge or they will not be accounted for and will affect predictions for interactions.

Step 4. Add charge.

• Add charges Tools > Structure Editing > Add charge Typically use AM1-BCC
• You need to be careful about selecting charge because this will affect predictions for interactions (i.e. Coulomb's Law). Read paper corresponding to your PDB stucture to determine conditions of purification and proper protonation. In the case of 6UZW our paper of reference is: https://doi.org/10.1038/s41467-020-14321-0

Pose Reprodution Flexible, Fixed-anchor, rigid