Identification of Invariant Core Positions

Perform iterated rounds of structural superposition to identify the most invariant region in an aligned set of protein structures.

core.find(...)

# S3 method for pdbs
core.find(pdbs, shortcut = FALSE, rm.island = FALSE,
          verbose = TRUE, stop.at = 15, stop.vol = 0.5,
          write.pdbs = FALSE, outpath="core_pruned",
          ncore = 1, nseg.scale = 1, progress = NULL, ...)

# S3 method for default
core.find(xyz, ...)

# S3 method for pdb
core.find(pdb, verbose=TRUE, ...)

Arguments

pdbs	a numeric matrix of aligned C-alpha xyz Cartesian coordinates. For example an alignment data structure obtained with `read.fasta.pdb` or `pdbaln`.
shortcut	if TRUE, remove more than one position at a time.
rm.island	remove isolated fragments of less than three residues.
verbose	logical, if TRUE a “core\_pruned” directory containing ‘core structures’ for each iteraction is written to the current directory.
stop.at	minimal core size at which iterations should be stopped.
stop.vol	minimal core volume at which iterations should be stopped.
write.pdbs	logical, if TRUE core coordinate files, containing only core positions for each iteration, are written to a location specified by `outpath`.
outpath	character string specifying the output directory when `write.pdbs` is TRUE.
ncore	number of CPU cores used to do the calculation. `ncore>1` requires package ‘parallel’ installed.
nseg.scale	split input data into specified number of segments prior to running multiple core calculation. See `fit.xyz`.
progress	progress bar for use with shiny web app.
xyz	a numeric matrix of xyz Cartesian coordinates, e.g. obtained from `read.dcd` or `read.ncdf`.
pdb	an object of type `pdb` as obtained from function `read.pdb` with multiple frames (>=4) stored in its `xyz` component. Note that the function will attempt to identify C-alpha and phosphate atoms (for protein and nucleic acids, respectively) in which the calculation should be based.
...	arguments passed to and from functions.

Details

This function attempts to iteratively refine an initial structural superposition determined from a multiple alignment. This involves iterated rounds of superposition, where at each round the position(s) displaying the largest differences is(are) excluded from the dataset. The spatial variation at each aligned position is determined from the eigenvalues of their Cartesian coordinates (i.e. the variance of the distribution along its three principal directions). Inspired by the work of Gerstein et al. (1991, 1995), an ellipsoid of variance is determined from the eigenvalues, and its volume is taken as a measure of structural variation at a given position.

Optional “core PDB files” containing core positions, upon which superposition is based, can be written to a location specified by outpath by setting write.pdbs=TRUE. These files are useful for examining the core filtering process by visualising them in a graphics program.

Value

Returns a list of class "core" with the following components:

volume

total core volume at each fitting iteration/round.

length

core length at each round.

resno

residue number of core residues at each round (taken from the first aligned structure) or, alternatively, the numeric index of core residues at each round.

step.inds

atom indices of core atoms at each round.

atom

atom indices of core positions in the last round.

xyz

xyz indices of core positions in the last round.

c1A.atom

atom indices of core positions with a total volume under 1 Angstrom\^3.

c1A.xyz

xyz indices of core positions with a total volume under 1 Angstrom\^3.

c1A.resno

residue numbers of core positions with a total volume under 1 Angstrom\^3.

c0.5A.atom

atom indices of core positions with a total volume under 0.5 Angstrom\^3.

c0.5A.xyz

xyz indices of core positions with a total volume under 0.5 Angstrom\^3.

c0.5A.resno

residue numbers of core positions with a total volume under 0.5 Angstrom\^3.

References

Grant, B.J. et al. (2006) Bioinformatics 22, 2695--2696.

Gerstein and Altman (1995) J. Mol. Biol. 251, 161--175.

Gerstein and Chothia (1991) J. Mol. Biol. 220, 133--149.

Note

The relevance of the ‘core positions’ identified by this procedure is dependent upon the number of input structures and their diversity.

Author

Barry Grant

Examples

if (FALSE) {
##-- Generate a small kinesin alignment and read corresponding structures
pdbfiles <- get.pdb(c("1bg2","2ncd","1i6i","1i5s"), URLonly=TRUE)
pdbs <- pdbaln(pdbfiles)

##-- Find 'core' positions
core <- core.find(pdbs)
plot(core)

##-- Fit on these relatively invarient subset of positions 
#core.inds <- print(core, vol=1)
core.inds <- print(core, vol=0.5)
xyz <- pdbfit(pdbs, core.inds, outpath="corefit_structures")

##-- Compare to fitting on all equivalent positions
xyz2 <- pdbfit(pdbs)

## Note that overall RMSD will be higher but RMSF will
##  be lower in core regions, which may equate to a
##  'better fit' for certain applications
gaps <- gap.inspect(pdbs$xyz)
rmsd(xyz[,gaps$f.inds])
rmsd(xyz2[,gaps$f.inds])

plot(rmsf(xyz[,gaps$f.inds]), typ="l", col="blue", ylim=c(0,9))
points(rmsf(xyz2[,gaps$f.inds]), typ="l", col="red")
}

if (FALSE) {
##-- Run core.find() on a multimodel PDB file
pdb <- read.pdb('1d1d', multi=TRUE)
core <- core.find(pdb)

##-- Run core.find() on a trajectory
trtfile <- system.file("examples/hivp.dcd", package="bio3d")
trj <- read.dcd(trtfile)

## Read the starting PDB file to determine atom correspondence
pdbfile <- system.file("examples/hivp.pdb", package="bio3d")
pdb <- read.pdb(pdbfile)

## select calpha coords from a manageable number of frames
ca.ind <- atom.select(pdb, "calpha")$xyz
frames <- seq(1, nrow(trj), by=10)

core <- core.find( trj[frames, ca.ind], write.pdbs=TRUE )

## have a look at the various cores "vmd -m core_pruned/*.pdb"

## Lets use a 6A^3 core cutoff
inds <- print(core, vol=6)
write.pdb(xyz=pdb$xyz[inds$xyz],resno=pdb$atom[inds$atom,"resno"], file="core.pdb")


##- Fit trj onto starting structure based on core indices
xyz <- fit.xyz( fixed = pdb$xyz,
               mobile = trj,
               fixed.inds  = inds$xyz,
               mobile.inds = inds$xyz)

##write.pdb(pdb=pdb, xyz=xyz, file="new_trj.pdb")
##write.ncdf(xyz, "new_trj.nc")

}