hello. i have finished running the ensemble docking with ligand library. what are the next step of computational methods or other methods available to prove the top scored molecules likely to be potent other than Biological testing and molecular dynamics?
A method which i came across is to compare the struture of the known inhibitors and the top scored moelcules. is there any other validation methods to test the top scored ones?
" comparison of the structure of the known inhibitors and the top scored molecules " is also known as Pharmacophore modelling ( molecules with same chemical features are hypothesized to have same biological effect). But, in case of pharmacophore modelling, ligand library is first screened through hypothesis (containing chemical features of known inhibitors) and then the molecules passing the hypothesis are docked. Since you have already docked the molecules i am not sure how many molecules you will retrieve if you develop hypothesis now. Anyway, even if you do that , there's no other method to prove the potency other than biological testing/ molecular dynamics. Molecular dynamics is the least you can do.
First, there is no one to one correlation between biological activity and the docking energies. However, you can perform free binding energy calculations for the top scored molecules. Second, there is no substitute to the bioligical validation.
It is better to look for the conserved interactions or the frequent interaction pattern of the known inhibitors rather, than the structure of hits.
Mohsin Yousuf Lone thanks. could you detail about the conserved interaction thing or suggest any article for that. many thanks
Goutham Rajendran Experimentally determined (XRD, NMR) unaltered interaction/s between inhibitor/s and amino acid/s of the protein are called conserved interactions.
- Badges
- Science topic
- Similar topics
- Chemistry
- Theoretical Chemistry
- Computational Chemistry
- Molecular Dynamics