Protein Sequence Analysis Protein Sequence Analysis Domain review - - PowerPoint PPT Presentation

Protein Sequence Analysis Protein Sequence Analysis

Domain review Domain review

ß ß What is a domain?

What is a domain?

ß ß Part of a sequence that can fold independently, and is Part of a sequence that can fold independently, and is present in other sequences as well present in other sequences as well

Domain Search Domain Search

ß ß Motifs (Regular expression & others)

Motifs (Regular expression & others)

ß ß Profiles

Profiles

ß ß Profile

Profile HMMs HMMs

PROSITE (Motif/Profiles) PROSITE (Motif/Profiles)

http://pfam.wustl.edu/ http://pfam.wustl.edu/

Also at Sanger Also at Sanger

http://hmmer.wustl.edu

HMMER programs

ß ß Hmmalign

Hmmalign

ß ß Align a sequence to an HMM Align a sequence to an HMM

ß ß Hmmbuild

Hmmbuild

ß ß Build a model from a multiple alignment Build a model from a multiple alignment

ß ß Hmmemit

Hmmemit

ß ß Emits a probabilistic sequence from an HMM Emits a probabilistic sequence from an HMM

ß ß Hmmpfam

Hmmpfam

ß ß Search PFAM with a sequence query Search PFAM with a sequence query

ß ß Hmmsearch

Hmmsearch

ß ß Search a sequence database with an HMM query Search a sequence database with an HMM query

Post-translational modification Post-translational modification

ß ß Residues undergo modification, usually by

Residues undergo modification, usually by addition of a chemical group. addition of a chemical group.

ß ß Key mechanism for signal transduction,

Key mechanism for signal transduction, and many other cellular functions and many other cellular functions

ß ß Some modifications might require single

Some modifications might require single residues (Ex: residues (Ex: phosphorylation phosphorylation). Others ). Others might require a pattern might require a pattern

Protein targeting Protein targeting

Protein targeting Protein targeting

ß ß In 1970, Gunter

In 1970, Gunter Blobel Blobel showed that showed that proteins have an N-terminal signal proteins have an N-terminal signal sequence which directs proteins to the sequence which directs proteins to the membrane. membrane.

ß ß Proteins have to be transported to other

Proteins have to be transported to other

• rganelles: nucleus, mitochondria,
• rganelles: nucleus, mitochondria,…

…

ß ß Can we computationally identify the

Can we computationally identify the ‘ ‘signal signal’ ’ which distinguishes the cellular which distinguishes the cellular compartment? compartment?

ß ß For

For transmembrane transmembrane proteins, can we proteins, can we predict the predict the transmembrane transmembrane, ,

• uter, and inner
• uter, and inner

regions? regions?

Multiple alignment tools Multiple alignment tools

Tools for secondary structure prediction

• Each residue must be

given a state: Helix, Loop, Strand

• HMMs/Neural

networks are used to predict

Next topic: Gene finding