SpikeMutator v1.5

SpikeMutator v1.5: COVID-19 Spike Mutator & Stability Energy Plotter

(c) 2021 Mohamed R. Smaoui, Hamdi Yahyaoui

Dept of Computer Science, College of Sciences, Kuwait University, Kuwait

mohamed.smaoui@ku.edu.kw

http://spikemutator.com

SpikeMutator is a program for generating PDB structures of desired mutations in the Spike protein of the SARS-CoV-2 virus. The mutations are applied on the 6VXX PDB template (closed spike conformation) and 6VYB PDB template (open spike conformation). The generated mutant structures undergo Molecular Dynamics Energy Minimization to relax any steric clashing. The program utilizes a dipolar-solvent water model to compute the solvation energy of the mutated structure and computes the Lennard-Jones and Coulomb potentials to determine the stability of the generated structures.

SpikeMutator runs as a command-line application on linux machines.

CITATION:

When citing this tool in any scientific publication please refer to it as:

Smaoui, M.R., Yahyaoui, H. Unraveling the stability landscape of mutations in the SARS-CoV-2 receptor-binding domain. Sci Rep 11, 9166 (2021). https://doi.org/10.1038/s41598-021-88696-5

INSTALLATION:

SpikeMutator utilizes the output of several programs to compute stability. In particular, it requires
the prior installation of SCWRL4, AQUASOL, PDB2PQR, GROMACS, gfortran, and Python2.7.

Step 1: 
	The first 3 software (SCWRL4, AQUASOL, and PDB2PQR) can be found in the "extra_tools" directory. 
	To use SCWRL4, you must register 
	for a free academic license at:
	http://dunbrack.fccc.edu/scwrl4/license/index.html

	unzip all 3 zip files

	$ cd extra_tools
	$ tar -xvf AquaSol_Complexes.tgz
	$ unzip pdb2pqr-1.7.zip
	$ unzip SCWRL4.zip

Step 2:	
	Install the AquaSol program that calculates Solvation energy execute the following 2 commands

	$ cd AquaSol_Complexes
	$ cd Aqua; sudo make clean
	$ cd ../src; sudo make clean
	$ cd ../Aqua; sudo make
	$ cd ../src; sudo make

Step 3:	
	Install SCWRL4.0 (after obtaining the license from 
	http://dunbrack.fccc.edu/scwrl4/license/index.html)

	$ cd SCWRL4.0
	$ ./install_Scwrl4_Linux
	
	Make sure you manually enter the full path to the SCWRL4.0 directory and update your 
	license information


Step 4:
	Open the SpikeMutator.py file and edit lines 4-8 to update the paths of SCWRL4, 
	AQUASOL, PDB2PQR, and GROMACS.

	If you don't have GROMACS installed, you can download the latest version of GROMACS from: 
	http://www.gromacs.org/Downloads

CLOSED SPIKE CONFORMATION:

USAGE 1: Generate the PDB structure for 1 mutation on the closed Spike trimer

	$ python SpikeMutator.py -p position -m AAmutation -c closed
		-p position: the residue (amino acid) position you want to mutate
		-m AAmutation: the amino acid mutation you want to replace position p with.
		   This is a letter. ex. Alanine is A
		-c conformation: closed will perform the muations on the 6VYB pdb template

	This commands performs a single point mutation on the closed spike protein trimer structure
	and generates a pdb file of the mutant trimer. 
	
	
	
USAGE 2: Generate the thermodynamic energy values for a closed mutant spike trimer

	$ python SpikeMutator.py -p position -m AAmutation -c closed -a energy
		-p position: the residue (amino acid) position you want to mutate
		-m AAmutation: the amino acid mutation you want to replace position p with.
		   This is a letter. ex. Alanine is A
		-c conformation: closed will perform the muations on the 6VYB pdb template
		-a energy: this flag instructs the program to calculate Coulomb, LJ and Solvation energies

	This commands performs a single point mutation on the closed spike protein trimer structure,
	and returns the Coulomb, LJ, and Solvation energies of the mutant spike. 

OPEN SPIKE CONFORMATION:

USAGE 3: Generate the PDB structure for 1 mutation on the open Spike trimer

	$ python SpikeMutator.py -p position -m AAmutation -c open
		-p position: the residue (amino acid) position you want to mutate
		-m AAmutation: the amino acid mutation you want to replace position p with.
		   This is a letter. ex. Alanine is A
		-c conformation: open will perform the muations on the 6VXX pdb template
	
	This commands performs a single point mutation on the open spike protein trimer structure
	and generates a pdb file of the mutant trimer. 
	
	
USAGE 4: Generate the thermodynamic energy values for a open mutant spike trimer

	$ python SpikeMutator.py -p position -m AAmutation -c open -a energy
		-p position: the residue (amino acid) position you want to mutate
		-m AAmutation: the amino acid mutation you want to replace position p with.
		   This is a letter. ex. Alanine is A
		-c conformation: open will perform the muations on the 6VXX pdb template
		-a energy: this flag instructs the program to calculate Coulomb, LJ and Solvation energies

	This commands performs a single point mutation on the open spike protein trimer structure,
	and returns the Coulomb, LJ, and Solvation energies of the mutant spike. 

COMPUTED STRUCTURES

The 3D PDB structures of all single point mutations in the RBD region have been pre-computed and can be found here: https://drive.google.com/drive/folders/1czrFHH-OZ5c8jzz-x2cDgwIeTjeK0Mzd?usp=sharing