| |
[摘要]：affinity calcns. remain challenging and enrichment rates of in silico screening methods unsatisfactory. Inadequate treatment of induced fit effects is one major shortcoming of existing in silico screening methods. Here the authors investigate enrichment rates of rigid-, soft- and flexible-receptor models for 12 diverse receptors using libraries contg. up to 13,000 mols. For the rigid-receptor model, the authors obsd. high enrichment (EF1 > 20) only for four target proteins. A soft-receptor model showed improved docking rates at the expense of reduced enrichment rates. A flexible side-chain model with flexible increased both binding propensity and enrichment rates: EF1 values increased by ~35% on av. with respect to rigid docking. The authors find on av. 4 known ligands in the top 10 mols. in the rank-ordered databases for the receptors investigated. |
|
