Homology modelling and structural comparisons Flashcards
Define Homolog
Two genes, proteins or other biological characters that are related by evolution
Define Ortholog
Two homologs that share a common ancestor prior to one or more speciation events
Define Paralogs
Two homologs that arose from one or more gene duplication events
What are two amino acids which are rarely replaced by others?
Trp and Cys
What is typical when protein sequences are more than 40% identical?
- most secondary structures are conserved, but lengths of the helices, sheet and strands may differ
- Most core hydrophobic residues are conserved, but not identical
- Loop regions are more likely to change than regions with regular secondary structure
- Surface residues are more likely to change than interior hydrophobic residues.
Give an example of convergent protein evolution
Subtilisin and chymotrypsin have different folds, but their active sites have identical residues.
How are Polyphen scores used?
Computer generated scores to predict the impact of a genetic mutation on the protein structure and function. It may assist with diagnosis and treatment of the disease, but it is based on conjecture so should not be the sole basis for action.
What is a prerequisite to ensure homology modeling of a mutation can work?
- the 3D structure of a homologous protein must have been previously determined by X-ray or electron crystallography, NMR or Cryo-EM.
What is Alphafold?
It is an AI program which predicts protein structure form protein sequence. It requires multiple sequence alignment of the residues.
It can fail by not taking into account ion binding
Co-variance in proteins
It is a method to predict protein structure based on the co-evolution of different protein sequences, since changes in one residue may require change in another residue in close proximity to maintain the protein’s stability.
RMSD
The average distance between equivalent atoms in two 3D structures
