DockEvolve by DeepFriedPancake

In silico Directed Evolution by Docking and Molecular Mechanics

Directed evolution of FtAlkB, Alkane monooxygenase extracted Fontimonas Thermophilia (PDB: 8f6t) for optimizing its ability to process fluoroalkanes. Originally an unconventional capstone project for CHEM 4055 - Enzyme Design In VR.

Inspired by [1], which concludes with quote: "Result offers researchers a new model of breaking C-F bonds and it has shown to be amenable to directed evolution, opening up opportunities for future research".

How to use

• Install gnina
  • It requires Linux so if you are on Windows use WSL2 with Ubuntu as distribution of choice
• Install python packages: pip install biopython OpenMM tabulate jupyter
  • It is recommended install these in a venv
• From jupyter lab, open dock_scan.ipynb
  • Create a .env and in it, set a GNINA_LOCATION, of where you installed gnina
    (The directory if installed by a raw git pull to file system, e.g. "/home/username/dock/gnina". If installed by apt/apt-get as a packaged command, just do "gnina")
  • Adjust parameters, you can even try evolving a different enzyme/substrate system
  • Run it

Sample result

Source citations and inspriations

Original experimental paper:
[1] Fontimonas thermophila Alkane Monooxygenase (FtAlkB) Is an Alkyl Fluoride Dehalogenase

Structure of FtAlkB:
[2] Structural basis for enzymatic terminal C–H bond functionalization of alkanes
UniProt and PDB, having above as primary citation

CNN_VS score of Gnina:
[3] CACHE Challenge #1: Docking with GNINA Is All You Need

Created by DeepFriedPancakes/PresidentKevvol 🥞 @ The Hornet's Nest