ProtoScreen™ is a robust virtual screening application developed as part as ProtoDiscovery™ software platform.
ProtoScreen™ is a multiconfomer docking program in which confomers are fitted to an active site using a Gaussian scoring function. Poses are then optimised and scored in the context of the ProtoScore™ predictive affinity function. Pre-computed confomers in the ProtoDiscovery™ Compound Database [PCD] enable a rapid screening rate of seconds per compound.
ProtoScreen™ has been subjected to extensive biological validation with excellent hit rates and enrichments determined for many targets.
ProtoScreen™ has been used successfully to identify novel ligands for many targets including a number of GPCRs, for both in-house and partner driven projects. The following tables show relevant in vitro results for some ProtoScreen™ campaigns
Enzyme and Nuclear Receptor Targets | Program | In silico screen size[1] | No. of compounds tested | No. of hits (inhibition @10µM) | Best hit(% inhibition) | Hit rate | Best hit Ki (nM) | Novelty[2] |
---|---|---|---|---|---|---|---|
[1] Size of PCD at time of screening; [2] % of novel hits based on SciFinder® searches | |||||||
Enzyme Target 1 | ~1.2 M | 43 | 24 | 75% | 52% | 3100 | 87% |
Nuclear Receptor | ~1.2 M | 51 | 17 | 100% | 33% | 490 | 100% |
Enzyme Target 2 | 2.5 M | 31 | 6 | 100% | 19% | 5500 | 84% |
Enzyme Target 3 | 3 M | 140 | 14 | 100% | 10% | 88 | 100% |
Enzyme Target 4 | 3M | 30 | 2 | 80% | 7% | 6000 | 100% |
ProtoScreen™ has also been applied systematically to five GPCR models. From the resulting in vitro data and activity profiles novel hits have been obtained which have been used as the basis for subsequent medicinal chemistry programs.
GPCR Targets | Program | In silico screen size[1] | No. of compounds tested | No. of hits (inhibition @10µM) | Best hit(% inhibition) | Hit rate | Best hit Ki (nM) | Novelty[2] |
---|---|---|---|---|---|---|---|
[1] Size of PCD at time of screening; [2] % of novel hits based on SciFinder® searches | |||||||
Target 1 agonist | ~2.5 M | 51 | 37 | 100% | 65% | 5 | 65% |
Target 2 agonist | ~3 M | 88 | 18 | 77% | 20% | 5500 | 100% |
Target 3 antagonist | ~3 M | 67 | 8 | 100% | 12% | 2500 | 75% |
Target 4 antagonist | ~3 M | 11 | 5 | 98% | 45% | 90 | 100% |
Target 5 agonist | ~3M | 28 | 8 | 100% | 29% | tbc | 100% |
Prosarix offer ProtoScreen™ as a service for structure based design projects.
©Prosarix 2007-2020
℅ RxCelerate Ltd, Moneta B280, Babraham Research Park, Cambridge, CB22 3AT ¦ +44 (0)1223 839557 ¦ contact@prosarix.com ¦ legal