• PDB - Protein Data Bank• SCOP – Protein structure classification • CATH – Protein structure classification • genTHREADER – 3D structure prediction• Swiss-Model – 3D structure prediction• ModBase - A database of 3D struc.

Predict.

Protein Structure Prediction II

PDB fileAccession number

Java based visualization tools

Structural Classification

PDB provides the atomic coordinates of the structure :

Which can be viewed by different visualization tools

SCOP: Structural Classification of Proteins

http://scop.mrc-lmb.cam.ac.uk/scop/

•Based on known protein structures

•Manually created by visual inspection

•Hierarchical database structure:–Class, Fold, Superfamily, Family, Protein

and Species

Parents of node

Childrenof node

Node

Parents of node

Childrenof node

Node

CATH: Protein Structure Classificationby Class, Architecture, Topology and Homology

http://www.cathdb.info/

•Class: The secondary structure composition: mainly-alpha, mainly-beta and alpha-beta.

• Architecture: The overall shape of the domain structure. Orientations of the secondary structures : e.g. barrel or 3-layer sandwich.

• Topology: Structures are grouped into fold groups at this level depending on both the overall shape and connectivity of the secondary structures.

•Homologous Superfamily: Evolutionary conserved structures

CATH: Protein Structure Classificationby Class, Architecture, Topology and Homology

genTHREADER

Input sequence

Type of Analysis

(PSIPRED,MEMSAT,

genTHREAD)

http://bioinf.cs.ucl.ac.uk/psipred/psiform.html

GenTHREADEROutput

GenTHREADEROutput

The output sequences show some extent of sequence homologyBut high level of secondary structure conservation

SWISS-MODEL

An automated protein modeling server.

http://swissmodel.expasy.org/

SWISS-MODEL• The SWISS-MODEL algorithm can be divided into

three steps:

1.Search for suitable templates: the server finds

all similarities of a query sequence to sequences

of known structure. It uses the BLASTP2 program

with the ExNRL-3D database (a derivative of PDB

database, specified for SWISS-MODEL). You get

these partial results as a SwissModel TraceLog

file.

2.Check sequence identity with target: All templates

with sequence identities above 25% are selected

3.Create the model using the ProModII program. You

get this as a SwissModel-Model file.

SWISS-MODEL

Get PDB file by E-mail

Load to J-Mol

Single StructureHomology Modeling

Swiss-Model file

Structures used for the homology

model

query

Comparative Modeling• Accuracy of the comparative model is related to the sequence identity on which it is based

>50% sequence identity = high accuracy 30%-50% sequence identity= 90% modeled

<30% sequence identity =low accuracy (many errors)

ModBaseA Homology Model Database

http://modbase.compbio.ucsf.edu/modbase-cgi/index.cgi

Ligand Binding Site

Excersize The sequence below belongs to the Prion that causes the “mad cow” disease. This protein becomes toxic

when it gets into the brain and misfolds causing native cellular prions to deform and aggregate. In structural terms, the prion toxicity in leaded by a folding change into an instable structure.

 

>PRION_1ag2

GLGGYMLGSAMSRPMIHFGNDWEDRYYRENMYRYPNQVYYRPVDQYSNQNNFVHDCVNITIKQHTVTTTTKGENFTETDVKMMERVVEQMCVTQYQKESQAYY

 

Use PSIpred, geneTHREADER and PROFsec in order to predict its secondary and tertiary structures. Based on the secondary and tertiary structure predictions

1. Can you suggest the region which could be responsible for the structural instability?

2. What is the secondary structure in the real solved structure?

3. What is the expected structural change in this region?

 

PSIPRED

geneTHREADER

PROFsec

PROFsec

Answer : alpha helix geneTHREADER turn into B-sheet PSIPRED anf PROFsec, prediction in this area are not consistent in the different tools.