foldx.mut: Compute Changes in Stability (DDG)

In ptm: Analyses of Protein Post-Translational Modifications

Compute Changes in Stability (DDG)

Description

Computes changes in the stability of a protein after a residue mutation using a force-field approach.

Usage

foldx.mut(pdb, ch, pos, newres = "", pH =7, method = "buildmodel", keepfiles = FALSE)

Arguments

pdb	the 4-letter identifier of a PDB structure or the path to a PDB file.
ch	a letter identifying the chain of interest.
pos	the position, in the primary structure, of the residue to be mutated.
newres	the one letter code of the residue to be incorporated. When a value is not entered for this parameter, then the function will compute DDG for the mutation to any possible amino acid (including phosphoserine, phosphothreonine, phosphotyrosine and hydroxiproline in the case of the 'positionscan' method).
pH	a numeric value between 0 and 14.
method	a character string specifying the approach to be used; it must be one of 'buildmodel', 'positionscan'.
keepfiles	logical, when TRUE the repaired PDB file is saved in the working directory.

Details

Two computational approaches for prediction of the effect of amino acid changes on protein stability are implemented. FoldX (buildmodel and positionscan methods) uses a force field approach and although it has been proved to be satisfactorily accurate, it is also a time-consuming method. An alternative much faster is I-Mutant, a method base on machine-learning

Value

The function computes and returns the DDG (kcal/mol) for the requested residue change, defined as DDG = DGmt - DGwt, where DG is the Gibbs free energy for the folding of the protein from its unfolded state. Thus, a positive value means a destabilizing effect, and vice versa.

Author(s)

Juan Carlos Aledo

References

Schymkowitz et al (2005) Nucl. Ac. Res. 33:W382-W388.

See Also

imutant(), ddG.profile()

Examples

## Not run: foldx.mut('1aaq', 'A', 45, 'R')

ptm documentation built on Aug. 7, 2022, 5:05 p.m.