what do you ask yourself when analysing a protein?
Significant sequence similarity (sequence conservation) indicating membership to a protein family
do they have motifs that suggest a specific function?
do they contain known protein domains?
similar/identical 3D structures
agreeing (conserved) expression patterns
interaction partners present / conservation of interaction networks
how can you determine 3D structures?
X-ray
NMR
3d-Electron microscopy (Cyro-EM)
what is the approach topredict 3D Models?
What can AlphaFold do?
fast and accurate 3D structure prediction
Why is using 3D strcutures helpul?
most natural way to look at proteins
similarity in 3D strcutures can be intepreted as siilaity of function
even highly diverged proteins can assume the same 3D strcuture
considerably few proteins have an experimentally determined 3D structure, and this willlikely not change
homology modelling is frequently used to predict the 3D strcuture of a protein based on known structures of related proteins
de novo structure prediction tools help when no structure of a related protein is avaiable
Alphafold 2 opens the filed to large-scale predictions
What can you do using Interpro scan?
fast public server to predict families etc.
what is intrisnic information?
information that can be extracted from the sequence itself
amino acid composition
low complexity region
hydrophobicty
requires priot biochemical knowledge too compute features such as charge, isoelectric point, size
commonly used for hydrophpbicity plots
indicative of exposed and burried residues in folded proteins
help to identify transmembrane regions and signali peptided
what is extrinsic information?
Information that is generated by comparing the sequence with others
local similarity to an evolutionary related sequence
conserved subsequences of identical length
conserved subsequences of variable length
structural similarity
How can i eaisly to check if the function changed?
Blosum 62
what are protein mortifs?
short linear sequences that serve a specific function for the protein, but will not be stable or fold independent of the rest of chain
often represented as regular expression
protein-protein interaction, logad interactions, cleavage sites, targeting
can we use sequence motifs for classification?
what is the goal of a multipe sequence alignment?
describe a functional evolutionary entity, e.g. a protein binding site, a functional doman, an entire gene, a functional pathway by capturing its characteristic properties
what should a model be?
represent an entity in a structured manner highlighting relevant characteristics and, at the same time, ignore similarities due to chance
describe the variability between different instances of the modelled entity
help to classify novel members of the entitity from the pool of candidates
identify outliers that differ more than exprected from average instance
Zuletzt geändertvor 10 Tagen