Impact of ligand protonation on virtual screening against beta-secretase (BACE1).
Structure-based virtual screens were carried out against beta-secretase (BACE1) to investigate the impact of ligand protonation on screening efficacy. A comparative evaluation of the performance and its dependence on ligand protonation states docking by Surflex, eHiTS, GOLD, and FlexX-Pharm was performed. Virtual screening performed by FlexX-Pharm (EF(1%)=69) and Surflex (EF(1%)=58) provided the best efficiency. Screening protocols by FlexX-Pharm and GOLD were affected by ligand protonation, while performance of Surflex did not depend on ligand protonation.
Polgar
Tímea
T
Gedeon Richter Plc, P.O. Box 27, Budapest, Hungary.
Magyar
Csaba
C
Simon
Istvan
I
Keserü
György M
GM
D000465:Algorithms; D053829:Amyloid Precursor Protein Secretases / Q000737:chemistry* / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D018360:Crystallography, X-Ray; D004353:Drug Evaluation, Preclinical; D008024:Ligands; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011522:Protons; D012984:Software
D008024:Ligands; D011522:Protons; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases