computational chemistry

what is the benefit of using computational chemistry in HIT identification?

removes the need of purchasing huge libraries and screening many compounds as you work with predicted properties, which saves time, money, reagents

what is homology modelling?

this model predicts that proteins with similar amino acid sequence will fold in a similar way

when would homology modelling be considered?

if proteins cannot be purified or a crystal structure is not known

how would we find the cyrstal structure of a known protein?

go to a software known as PDB and search the protein. download the coordinates for the crystal structure, and conduct virtual screening

how can we predict the structure of a protein that we dont know the crystal structure of using homlogous modelling?

search the protein on the uniport database that will tell you the amino acid sequece of it usinf FASTA. using swissport- another software- you can try and predict the folding of the amino acid and the structure of the protein.

how can we predict the structure of a protein that we dont know the crystal structure of using alphafold?

search for the target protein and downlaod the structure and conduct virtual screening

why is alpha fold more accurate?

is is a structural database for protein folding and will tell you what areas of he predicted protein are likely to fold that way in terms of confidence and is very accurate

what happens in structure based virtual screening?

in this scenario the active site of the compound is known and you are screening different compound for the active site

what happens in ligand based virtual screening?

ligands that show activity are used to build a pharmacophore and libraries are screened to find new molecules that will match it

what is a true HIT compound?

changing the molecular structure will either increase or decrease the activity

in virtual screening how are the compounds scored?

using mathematical models like GOLD or YASRA that look at all interactions the compound has with the target.

during molecular docking why is it important to have a large surface area for binding?

allows the visualization of where the drugs would normally bind in their own freedom, and helps prevent identifying a false positive

when would steric terms be more important in the scoring ?

if the active site is deep into the grooves of the enzyme and positioning would be very important in binding

what are some drawback of virtual screening?

not realistic as other factors including membrane and water are not considered

what is the function of quantitative structure activity relationship QSAR?

tool that predicts how changing the chemical structure will result in an increase in decrease in activity