PHAR 202 - 2.5 Protein Bioinformatics

Databases from the NCBI (National Library of Medicine)

PubMed, PubChem, Books, BLAST, Protein, Structure

What is the NIH? (National Library of Medicine/National Center for Biotechnology Information)

US-based and publicly funded information service to advance science and health by providing access to biomedical and genomic information

What is the RCSB PDB

US data centre for the global PDB archive of 3D structure data for large biological molecules

What is ExPASy (Expert Protein Analysis System)

the bioinformatics resource portal of the Swiss Institute of Bioinformatics (SIB)

What is UniProt

a protein knowledgablebase

- provide info about protein function, names, taxonomy, subcellular localization, disease and variants, PTMs and processing, expression, interactions, structure, family and domains, sequence and isoforms, and similar proteins

What is PROSITE

Database for prediction of protein domains, families, and functional sites (PTMs)

What is the Protein Folding Problem

Predicting a protein's 3D structure from its primary amino acid sequence

Why are experimental methods (NMR, X-ray crystallography, cryo-EM) not always ideal for determining protein structure?

They are difficult, time consuming, and resource-intensive

What determines a protein's 3D structure

It’s primary amino acid sequence

How do proteins fold under physiological conditions?

They spontaneously fold into their native 3D structures

What evidence supports that the primary structure determines folding? (2)

Mutagenesis experiments show internal residues guide folding

Folding is largely driven by hydrophobic forces

What is AlphaFold?

A tool for predicting the structure of protein complexes, including proteins, nucleic acids, small molecules, ions and modified residues

The AlphaFold DB provides predicted structures for broad coverage of...

UniProt entires

What does pLDDT > 90 mean?

Very high confidence

What does 90 > pLDDT > 70 mean?

High confidence

What does 70 > pLDDT > 50 mean?

Low confidence

What does pLDDT < 50 mean?

Very low confidence

What does PTM (predicted template modeling) > 0.5 mean?

The overall predicted fold may be similar to the true structure

What does iPTM > 0.8 mean

Confident high-quality predictions

What does 0.6 < iPTM < 0.8 mean

Gray zone -- moderate confidence

What does iPTM < 0.6 mean

Likely a failed prediction

What does pLDDT measure?

Confidence for each residue (local accuracy) in the predicted structure

What is the scale for pLDDT?

0-100, where higher values mean higher confidence

What does PTM measure?

Confidence in the overall fold / shape of the entire predicted structure

What does iPTM measure?

Confidence in the relative orientation and interactions between proteins in a complex