Name
Abstract | ||
|---|---|---|
In a first step in the discovery of novel potent inhibitor structures for the PDE4B family with limited side effects, we present a protocol to rank newly designed molecules through the estimation of their IC[Formula: see text] values. Our protocol is based on reproducing the linear relationship between the logarithm of experimental IC[Formula: see text] values [[Formula: see text](IC[Formula: see text])] and their calculated binding free energies ([Formula: see text]). From 13 known PDE4B inhibitors, we show here that (1) binding free energies obtained after a docking process by AutoDock are not accurate enough to reproduce this linear relationship; (2) MM-GB/SA post-processing of molecular dynamics (MD) trajectories of the top ranked AutoDock pose improves the linear relationship; (3) by taking into account all representative structures obtained by AutoDock and by averaging MM-GB/SA computations on a series of 40 independent MD trajectories, a linear relationship between [Formula: see text](IC[Formula: see text]) and the lowest [Formula: see text] is achieved with [Formula: see text]. |
Year | DOI | Venue |
|---|---|---|
2017 | https://doi.org/10.1007/s10822-017-0024-7 | Journal of Computer-Aided Molecular Design |
Keywords | Field | DocType |
PDE4B,IC,50,Molecular docking,Molecular dynamics,MM-GB/SA | Protein ligand,Computational chemistry,Chemistry,Molecular dynamics,Bioinformatics,Logarithm,AutoDock | Journal |
Volume | Issue | ISSN |
31 | 6 | 0920-654X |
Citations | PageRank | References |
0 | 0.34 | 15 |
Authors | ||
4 | ||
Name | Order | Citations | PageRank |
|---|---|---|---|
| Gülşah Çifci | 1 | 0 | 0.34 |
| Viktorya Aviyente | 2 | 11 | 3.82 |
| E. Demet Akten | 3 | 0 | 0.34 |
| Gerald Monard | 4 | 4 | 1.65 |