/ 
Bio-Protease-1.092570
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/ Bio::Protease

NAME

Bio::Protease - Digest your protein substrates with customizable specificity

VERSION

version 1.092570

SYNOPSIS

use Bio::Protease;
my $protease = Bio::Protease->new(specificity => 'trypsin');

my $protein = 'MRAERVIKP';

# Perform a full digestion
my @products = $protease->digest($protein);

# products: ( 'MR', 'AER', 'VIKP' )

# Get all the siscile bonds.
my @sites = $protease->cleavage_sites($protein);

# sites: ( 2, 5 )

# Try to cut at a specific position.

@products = $protease->cut($protein, 2);

# products: ( 'MR', 'AERVIKP' )

WARNING: ALPHA CODE

This module is still in its infancy, and I might change its interface in the future (although I'm not planning to). Use it at your own discretion (but please do, and send feedback!).

DESCRIPTION

This module models the hydrolitic behaviour of a proteolytic enzyme. Its main purpose is to predict the outcome of hydrolitic cleavage of a peptidic substrate.

The enzyme specificity is currently modeled for 36 enzymes/reagents. This models are somewhat simplistic as they are largely regex-based, and do not take into account subtleties such as kinetic/temperature effects, accessible solvent area, secondary or tertiary structure elements. However, the module is flexible enough to allow the inclusion of any of these effects by subclassing from the module's interface, Bio::ProteaseI. Alternatively, if your desired specificity can be correctly described by a regular expression, you can pass it as a string the specificity attribute at construction time. See specificity below.

SEE ALSO

  • PeptideCutter

    This module's idea is largely based on Expasy's PeptideCutter (http://www.expasy.ch/tools/peptidecutter/). For more information on the experimental evidence that supports both the algorithm and the specificity definitions, check their page.

ATTRIBUTES

specificity

Set the enzyme's specificity. Required. Could be either of:

  • an enzyme name: e.g. 'enterokinase'

    my $enzyme = Bio::Protease->new(specificity => 'enterokinase');

    There are currently definitions for 36 enzymes/reagents. See Specificities.

  • an array reference of regular expressions:

    my $motif = ['MN[ED]K[^P].{3}'],

my $enzyme = Bio::Protease->new(specificity => $motif);

    The motif should always describe an 8-character long peptide. When a an octapeptide matches the regex, its 4th peptidic bond (ie, between the 4th and 5th letter) will be marked for cleaving or reporting.

    For example, the peptide AMQRNLAW is recognized as follows:

    .----..----.----..----. .-----.-----.-----.-----.
| A  || M  | Q  || R  |*|  N  |  L  |  A  |  W  |
|----||----|----||----|^|-----|-----|-----|-----|
| P4 || P3 | P2 || P1 ||| P1' | P2' | P3' | P4' |
'----''----'----''----'|'-----'-----'-----'-----'
                  cleavage site

    Some specificity rules can only be described with more than one regular expression (See the case for trypsin, for example). To account for those cases, the array reference could contain an arbitrary number of regexes, all of which should match the given octapeptide.

    In the case your particular specificity rule requires an "or" clause, you can use the "|" separator in a single regex.

Specificities

This class attribute contains a hash reference with all the available regexep-based specificities. The keys are the specificity names, the value is an arrayref with the regular expressions that define them.

my @protease_pool = do {
    Bio::Protease->new(specificity => $_)
        for keys %{Bio::Protease->Specificities};
}

As a rule, all specificity names are lower case. Currently, they include:

  • arg-cproteinase

  • asp-n_endopeptidase

  • asp-n_endopeptidase_glu

  • bnps_skatole

  • caspase_1

  • caspase_2

  • caspase_3

  • caspase_4

  • caspase_5

  • caspase_6

  • caspase_7

  • caspase_8

  • caspase_9

  • caspase_10

  • chymotrypsin

  • chymotrypsin_low

  • clostripain

  • cnbr

  • enterokinase

  • factor_xa

  • formic_acid

  • glutamyl_endopeptidase

  • granzymeb

  • hydroxylamine

  • iodosobenzoic_acid

  • lysc

  • lysn

  • ntcb

  • pepsin_ph1.3

  • pepsin

  • proline_endopeptidase

  • proteinase_k

  • staphylococcal_peptidase i

  • thermolysin

  • thrombin

  • trypsin

For a complete description of their specificities, you can check out http://www.expasy.ch/tools/peptidecutter/peptidecutter_enzymes.html, or look at the regular expressions of their definitions in this same file.

METHODS

digest

Performs a complete digestion of the peptide argument, returning a list with possible products. It does not do partial digests (see method cut for that).

my @products = $enzyme->digest($protein);

cut

Attempt to cleave $peptide at the C-terminal end of the $i-th residue (ie, at the right). If the bond is indeed cleavable (determined by the enzyme's specificity), then a list with the two products of the hydrolysis will be returned. Otherwise, returns false.

my @products = $enzyme->cut($peptide, $i);

cleavage_sites

Returns a list with siscile bonds (bonds susceptible to be cleaved as determined by the enzyme's specificity). Bonds are numbered starting from 1, from N to C-terminal. Takes a string with the protein sequence as an argument:

my @sites = $enzyme->cleavage_sites($peptide);

is_substrate

Returns true or false whether the peptide argument is a substrate or not. Esentially, it's equivalent to calling cleavage_sites in boolean context, but with the difference that this method short-circuits when it finds its first cleavable site. Thus, it's useful for CPU-intensive tasks where the only information required is whether a polypeptide is or not a substrate of a particular enzyme.

AUTHOR

Bruno Vecchi <vecchi.b@gmail.com>

COPYRIGHT AND LICENSE

This software is copyright (c) 2009 by Bruno Vecchi.

This is free software; you can redistribute it and/or modify it under the same terms as the Perl 5 programming language system itself.