Protein flexibility in virtual screening: the BACE-1 case study.

ABSTRACT: Simulating protein flexibility is a major issue in the docking-based drug-design process for which a single methodological solution does not exist. In our search of new anti-Alzheimer ligands, we were faced with the challenge of including receptor plasticity in a virtual screening campaign aimed at finding new β-secretase inhibitors. To this aim, we incorporated protein flexibility in our simulations by using an ensemble of static X-ray enzyme structures to screen the National Cancer Institute database. A unified description of the protein motion was also generated by computing and combining a set of grid maps using an energy weighting scheme. Such a description was used in an energy-weighted virtual screening experiment on the same molecular database. Assessment of the enrichment factors

SUBMITTER: Cosconati S 

PROVIDER: S-EPMC3523752 | biostudies-literature | 2012 Oct

REPOSITORIES: biostudies-literature