Phyre2 - Structural Bioinformatics Group - Imperial College London

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Oct 2, 2013 (4 years and 1 month ago)

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Phyre2

Dr. Lawrence Kelley

Structural Bioinformatics Group

Imperial College London

SVYDAAAQLTADVKKDLRDSW

KVIGSDKKGNGVALMTTLFAD

NQETIGYFKRLGNVSQGMAND

KLRGHSITLMYALQNFIDQLD

NPDSLDLVCS…….

Predict the
3
D structure
adopted by a user
-
supplied
protein sequence

Phyre2

How does Phyre2 work?

ARDLVIPMIYCGHGY

Search the 10 million known
sequences for homologues
using PSI
-
Blast.

Phyre2

Homologous
sequences

User sequence

ARDLVIPMIYCGHGY

HMM

PSI
-
Blast

Phyre2

Hidden Markov model

Capture the mutational propensities at each position in the protein


An evolutionary fingerprint

User sequence

~
65
,
000
known
3
D structures

Phyre2

~ 65,000 known 3D structures

Phyre
2

~ 65,000 known 3D structures

Phyre2

HAPTLVRDC…….

Extract sequence

~ 65,000 known 3D structures

Phyre2

HAPTLVRDC…….

PSI
-
Blast

Extract sequence

~ 65,000 known 3D structures

Phyre2

HAPTLVRDC…….

HMM

PSI
-
Blast

Hidden Markov model

for sequence of KNOWN structure

Extract sequence

~
65
,
000
known
3
D structures

Phyre2

HMM

HMM

HMM

~ 65,000 hidden Markov models

~
65
,
000
known
3
D structures

Phyre2

Hidden Markov Model
Database of

KNOWN

STRUCTURES

ARDLVIPMIYCGHGY

HMM

PSI
-
Blast

Phyre
2

Hidden Markov model

Capture the mutational propensities at each position in the protein


An evolutionary fingerprint

ARDLVIPMIYCGHGY

HMM

PSI
-
Blast

Hidden Markov
Model DB of
KNOWN

STRUCTURES

HMM
-
HMM

matching

Phyre
2

Alignments of user sequence to known structures

ranked by confidence.

ARDL
--
VIPM
IY
CGHGY

AFDL
CD
LIPV
--
CGMAY

Sequence of known structure

ARDLVIPMIYCGHGY

HMM

PSI
-
Blast

Hidden Markov
Model DB of
KNOWN

STRUCTURES

HMM
-
HMM

matching

Phyre2

ARDL
--
VIPM
IY
CGHGY

AFDL
CD
LIPV
--
CGMAY

Sequence of known structure

3D
-
Model

ARDLVIPMIYCGHGY

HMM

PSI
-
Blast

Hidden Markov
Model DB of
KNOWN

STRUCTURES

HMM
-
HMM

matching

Phyre2

ARDL
--
VIPM
IY
CGHGY

AFDL
CD
LIPV
--
CGMAY

Sequence of known structure

Very powerful



able to reliably detect extremely

remote homology

Routinely creates accurate models even

w
hen sequence identity is <15%

3D
-
Model