Cleavage of polypeptide sequences

This functions cleave polypeptide sequences. Use cleavageSites to find the cleavage sites, cleavageRanges to find the cleavage ranges and cleave to get the cleavage products.

# S4 method for character
cleave(x, enzym = "trypsin", missedCleavages = 0,
                             custom = NULL, unique = TRUE)

# S4 method for AAString
cleave(x, enzym = "trypsin", missedCleavages = 0,
                            custom = NULL, unique = TRUE)

# S4 method for AAStringSet
cleave(x, enzym = "trypsin", missedCleavages = 0,
                               custom = NULL, unique = TRUE)

# S4 method for character
cleavageRanges(x, enzym = "trypsin", missedCleavages = 0,
                                     custom = NULL)

# S4 method for AAString
cleavageRanges(x, enzym = "trypsin", missedCleavages = 0,
                                    custom = NULL)

# S4 method for AAStringSet
cleavageRanges(x, enzym = "trypsin", missedCleavages = 0,
                                       custom = NULL)

# S4 method for character
cleavageSites(x, enzym = "trypsin", custom = NULL)

# S4 method for AAString
cleavageSites(x, enzym = "trypsin", custom = NULL)

# S4 method for AAStringSet
cleavageSites(x, enzym = "trypsin", custom = NULL)

Arguments

x

polypeptide sequences.

enzym

character, cleavage rule.

missedCleavages

numeric, number of missed cleavages.

custom

character, of length 1 or 2. Could be used to define own cleaveage rules. The first element would be the pattern and the optional second element would be an exception (non-cleavage) pattern. Perl-like regular expressions are supported, see gregexpr for details. If custom is set the enzym is ignored.

unique

logical, if TRUE all duplicated cleavage products per peptide are removed.

Value

cleave

If x is a character it returns a list of the same length as x. Each element contains a character vector with the corresponding cleavage products of the polypeptides. If x is an AAString or an AAStringSet an AAStringSet or an AAStringSetList instance of the same length as x is returned. Each element contains an AAString or an AAStringSet instance with the corresponding cleavage products of the polypeptides.

cleavageRanges

If x is a character it returns a list of the same length as x. Each element contains a two-column matrix with the start and end positions of the peptides. If x is an AAString or an AAStringSet instance an IRanges or an IRangesList of the same length as x is returned.

cleavageSites

Returns a list of the same length as x. Each element contains an integer vector with the cleavage positions.

Overview:

Input	cleave	cleavageRanges	cleavageSites
character	list of character	list of matrix	list of integer
AAString	AAStringSet	IRanges	list of integer
AAStringSet	AAStringSetList	IRangesList	list of integer

Details

The cleavage rules are taken from: https://web.expasy.org/peptide_cutter/peptidecutter_enzymes.html

Cleavage rules (cleavage between P1 and P1'):

Rule name	P4	P3	P2	P1	P1'	P2'	arg-c proteinase
-	-	-	R	-	-	asp-n endopeptidase	-
-	-	-	D	-	bnps-skatole-c	-	-
-	W	-	-	caspase1	F,W,Y,L	-	H,A,T
D	not P,E,D,Q,K,R	-	caspase2	D	V	A	D
not P,E,D,Q,K,R	-	caspase3	D	M	Q	D	not P,E,D,Q,K,R
-	caspase4	L	E	V	D	not P,E,D,Q,K,R	-
caspase5	L,W	E	H	D	-	-	caspase6
V	E	H,I	D	not P,E,D,Q,K,R	-	caspase7	D
E	V	D	not P,E,D,Q,K,R	-	caspase8	I,L	E
T	D	not P,E,D,Q,K,R	-	caspase9	L	E	H
D	-	-	caspase10	I	E	A	D
-	-	chymotrypsin-high	-	-	-	F,Y	not P
-		-	-	-	W	not M,P	-
chymotrypsin-low	-	-	-	F,L,Y	not P	-
-	-	-	W	not M,P	-		-
-	-	M	not P,Y	-		-	-
-	H	not D,M,P,W	-	clostripain	-	-	-
R	-	-	cnbr	-	-	-	M
-	-	enterokinase	D,E	D,E	D,E	K	-
-	factor xa	A,F,G,I,L,T,V,M	D,E	G	R	-	-
formic acid	-	-	-	D	-	-	glutamyl endopeptidase
-	-	-	E	-	-	granzyme-b	I
E	P	D	-	-	hydroxylamine	-	-
-	N	G	-	iodosobenzoic acid	-	-	-
W	-	-	lysc	-	-	-	K
-	-	lysn	-	-	-	-	K
-	neutrophil elastase	-	-	-	A,V	-	-
ntcb	-	-	-	-	C	-	pepsin1.3
-	not H,K,R	not P	not R	F,L	not P	pepsin	-
not H,K,R	not P	not R	F,L,W,Y	not P		-	not H,K,R
not P	F,L,W,Y	-	not P		-	not H,K,R	not P
F,L	-	not P	proline endopeptidase	-	-	not H,K,R	P
not P	-	proteinase k	-	-	-	A,E,F,I,L,T,V,W,Y	-
-	staphylococcal peptidase i	-	-	not E	E	-	-
thermolysin	-	-	-	not D,E	A,F,I,L,M,V	-	thrombin
-	-	G	R	G	-		A,F,G,I,L,T,V,M
A,F,G,I,L,T,V,W	P	R	not D,E	not D,E	trypsin	-	-
-	K,R	not P	-		-	-	W
K	P	-		-	-	M	R

Exceptions:

Rule name	Enzyme name	P4	P3	P2	P1	P1'	P2'
trypsin	-	-	C,D	K	D	-
	-	-	C	K	H,Y	-
	-	-	C	R	K	-
	-	-	R	R	H,R	-

Rule name	Enzyme name
arg-c proteinase	Arg-C proteinase
asp-n endopeptidase	Asp-N endopeptidase
bnps-skatole-c	BNPS-Skatole
caspase1	Caspase 1
caspase2	Caspase 2
caspase3	Caspase 3
caspase4	Caspase 4
caspase5	Caspase 5
caspase6	Caspase 6
caspase7	Caspase 7
caspase8	Caspase 8
caspase9	Caspase 9
caspase10	Caspase 10
chymotrypsin-high	Chymotrypsin-high specificity (C-term to [FYW], not before P)
chymotrypsin-low	Chymotrypsin-low specificity (C-term to [FYWML], not before P)
clostripain	Clostripain (Clostridiopeptidase B)
cnbr	CNBr
enterokinase	Enterokinase
factor xa	Factor Xa
formic acid	Formic acid
glutamyl endopeptidase	Glutamyl endopeptidase
granzyme-b	Granzyme B
hydroxylamine	Hydroxylamine
iodosobenzoic acid	Iodosobenzoic acid
lysc	LysC
lysn	LysN
neutrophil elastase	Neutrophil elastase
ntcb	NTCB (2-nitro-5-thiocyanobenzoic acid)
pepsin1.3	Pepsin (pH == 1.3)
pepsin	Pepsin (pH > 2)
proline endopeptidase	Proline-endopeptidase
proteinase k	Proteinase K
staphylococcal peptidase i	Staphylococcal Peptidase I
thermolysin	Thermolysin
thrombin	Thrombin
trypsin	Trypsin

Author

Sebastian Gibb <mail@sebastiangibb.de>

References

Gasteiger E., Hoogland C., Gattiker A., Duvaud S., Wilkins M.R., Appel R.D., Bairoch A.; "Protein Identification and Analysis Tools on the ExPASy Server". (In) John M. Walker (ed): The Proteomics Protocols Handbook, Humana Press (2005).
https://web.expasy.org/peptide_cutter/peptidecutter_enzymes.html

See also

AAString, AAStringSet, AAStringSetList, IRanges, IRangesList

Examples

library("cleaver")

## Gastric juice peptide 1 (UniProtKB/Swiss-Prot: GAJU_HUMAN/P01358)
gaju <- "LAAGKVEDSD"

cleave(gaju, "trypsin")
#> $LAAGKVEDSD
#> [1] "LAAGK" "VEDSD"
#> 
# $LAAGKVEDSD
# [1] "LAAGK" "VEDSD"

cleavageRanges(gaju, "trypsin")
#> $LAAGKVEDSD
#>      start end
#> [1,]     1   5
#> [2,]     6  10
#> 
# $LAAGKVEDSD
#      start end
# [1,]     1   5
# [2,]     6  10

cleavageSites(gaju, "trypsin")
#> $LAAGKVEDSD
#> [1] 5
#> 
# $LAAGKVEDSD
# [1] 5

cleave(gaju, "trypsin", missedCleavages=1)
#> $LAAGKVEDSD
#> [1] "LAAGKVEDSD"
#> 
# $LAAGKVEDSD
# [1] "LAAGKVEDSD"

cleavageRanges(gaju, "trypsin", missedCleavages=1)
#> $LAAGKVEDSD
#>      start end
#> [1,]     1  10
#> 
# $LAAGKVEDSD
#      start end
# [1,]     1  10

cleave(gaju, "trypsin", missedCleavages=0:1)
#> $LAAGKVEDSD
#> [1] "LAAGK"      "VEDSD"      "LAAGKVEDSD"
#> 
# $LAAGKVEDSD
# [1] "LAAGK" "VEDSD" "LAAGKVEDSD"

cleavageRanges(gaju, "trypsin", missedCleavages=0:1)
#> $LAAGKVEDSD
#>      start end
#> [1,]     1   5
#> [2,]     6  10
#> [3,]     1  10
#> 
# $LAAGKVEDSD
#      start end
# [1,]     1   5
# [2,]     6  10
# [3,]     1  10


cleave(gaju, "pepsin")
#> $LAAGKVEDSD
#> [1] "LAAGKVEDSD"
#> 
# $LAAGKVEDSD
# [1] "LAAGKVEDSD"
# (no cleavage)


## use AAStringSet
gaju <- AAStringSet("LAAGKVEDSD")

cleave(gaju)
#> AAStringSetList of length 1
#> [["LAAGKVEDSD"]] LAAGK VEDSD
# AAStringSetList of length 1
# [["LAAGKVEDSD"]] LAAGK VEDSD


## Beta-enolase (UniProtKB/Swiss-Prot: ENOB_THUAL/P86978)
enob <- "SITKIKAREILD"

cleave(enob, "trypsin")
#> $SITKIKAREILD
#> [1] "SITK" "IK"   "AR"   "EILD"
#> 
# $SITKIKAREILD
# [1] "SITK" "IK"   "AR"   "EILD"

cleave(enob, "trypsin", missedCleavages=2)
#> $SITKIKAREILD
#> [1] "SITKIKAR" "IKAREILD"
#> 
# $SITKIKAREILD
# [1] "SITKIKAR" "IKAREILD"

cleave(enob, "trypsin", missedCleavages=0:2)
#> $SITKIKAREILD
#> [1] "SITK"     "IK"       "AR"       "EILD"     "SITKIK"   "IKAR"     "AREILD"  
#> [8] "SITKIKAR" "IKAREILD"
#> 
# $SITKIKAREILD
# [1] "SITK"     "IK"       "AR"       "EILD"     "SITKIK"   "IKAR"
# [7] "AREILD"   "SITKIKAR" "IKAREILD"

## define own cleavage rule: cleave at K
cleave(enob, custom="K")
#> $SITKIKAREILD
#> [1] "SITK"   "IK"     "AREILD"
#> 
# $SITKIKAREILD
# [1] "SITK"   "IK"     "AREILD"

cleavageRanges(enob, custom="K")
#> $SITKIKAREILD
#>      start end
#> [1,]     1   4
#> [2,]     5   6
#> [3,]     7  12
#> 
# $SITKIKAREILD
#      start end
# [1,]     1   4
# [2,]     5   6
# [3,]     7  12

## define own cleavage rule: cleave at K but not if followed by A
cleave(enob, custom=c("K", "K(?=A)"))
#> $SITKIKAREILD
#> [1] "SITK"     "IKAREILD"
#> 
# $SITKIKAREILD
# [1] "SITK"     "IKAREILD"

cleavageRanges(enob, custom=c("K", "K(?=A)"))
#> $SITKIKAREILD
#>      start end
#> [1,]     1   4
#> [2,]     5  12
#> 
# $SITKIKAREILD
#      start end
# [1,]     1   4
# [2,]     5  12

cleavageSites(enob, custom=c("K", "K(?=A)"))
#> $SITKIKAREILD
#> [1] 4
#> 
# $SITKIKAREILD
# [1] 4