A Beginner’s Guide to Molecular Docking with Smina

A Beginner’s Guide to Molecular Docking with Smina
by Aouidate

Originally on Medium : Medium Article

Molecular docking is an essential technique in computational drug discovery, allowing us to predict how small molecules (ligands) interact with biological targets (proteins). With the rise of open-source tools, this field is more accessible than ever, even for undergraduate students. One such tool is Smina - a fork of AutoDock Vina with enhanced scoring and user features.

In this tutorial, we’ll walk through a beginner-friendly workflow for running molecular docking experiments with Smina.

Table of Contents

1. What is Molecular Docking?
2. Why Use Smina?
3. Setting Up Your Environment
4. Preparing the Protein and Ligand
5. Running Docking with Smina
6. Analyzing the Results
7. Tips and Best Practices
8. Further Reading

What is Molecular Docking?

Molecular docking simulates the interaction between a receptor (usually a protein) and a ligand (a small molecule or drug candidate). The goal is to predict the preferred orientation of the ligand when bound to the protein and to estimate the binding affinity.

Why Use Smina?

• Open Source: Smina is free and actively maintained.
• Improved Scoring: Better scoring functions than vanilla AutoDock Vina.
• Customizability: Allows user-defined scoring functions.
• Cross-Platform: Runs on Windows, macOS, and Linux.

Setting Up Your Environment

1. Install Smina

You can download from SourceForge or using conda:

conda install -c conda-forge smina

If downloaded from SourceForge, place the executable in a directory included in your $PATH.

2. Install Support Tools

• Open Babel: For format conversion (sudo apt install openbabel)
• PDBFixer or PyMOL: For protein preparation

Preparing the Protein and Ligand

1. Protein Preparation

• Download your protein structure (PDB format) from the Protein Data Bank.
• Remove water molecules and unwanted chains.
• Add hydrogens and assign correct protonation states (using PDBFixer, PyMOL, or Chimera).
• Save as PDBQT format (required by Smina):

  obabel protein.pdb -O protein.pdbqt
  

2. Ligand Preparation

• Draw or download your ligand structure.
• Convert to 3D, add hydrogens.
• Save as PDBQT:

  obabel ligand.sdf -O ligand.pdbqt --gen3d
  

Running Docking with Smina

Set the binding site (center and size) based on your protein structure (e.g., using PyMOL or Chimera to find the coordinates):

./smina -r protein.pdbqt -l ligand.pdbqt --center_x 10 --center_y 15 --center_z 20 --size_x 20 --size_y 20 --size_z 20 --out docked_ligand.pdbqt --log docking.log

• -r: receptor (protein)
• -l: ligand
• --center_* and --size_*: define the docking box
• --out: output file
• --log: log file

Analyzing the Results

• Use PyMOL, Chimera, or UCSF ChimeraX to visualize the docked poses.
• The log file provides binding affinity scores (in kcal/mol).
• Look for low (more negative) scores and reasonable binding modes.

Tips and Best Practices

• Always verify the preparation of your structures.
• Try multiple docking runs for reliability.
• Visual inspection is key—scores are not everything!
• Compare results with literature or experimental data when possible.

Further Reading

• Smina GitHub Repository
• AutoDock Vina Manual
• PyMOL Documentation
• Open Babel Documentation

Happy Docking! If you have questions or want to share your results, feel free to comment below or reach out.