Autodock Vina/UCSF Chimera
Avogadro 1.2 (http://avogadro.cc)
Autodock Vina 1.1.2
UCSF Chimera 1.13.1 (http://www.cgl.ucsf.edu/chimera/) with Vina interface plugin
Receptor Preparation (BACE_14 protein): DockPrep defaults as implemented in Chimera; AMBER FF14SB/Gasteiger charges
Ligand preparation: protonation for pH 7.4 followed by MMFF94 optimization in Avogadro
all ligands and water molecules are removed from the receptor structure (BACE_14 was used for all dockings). DockPrep plugin
of Chimera was used to prepare the structure using default settings.
The Vina search volume is defined based on the total overlap of disclosed BACE poses:
Center (x, y, z): 28.9, 4.9, 14.9; Size: 15.4, 13.4, 19.9A.
Default settings for Vina plugun were used elsewhere. Only the top scored pose was used for binding energy calculation.
N/A
No
BACE macrocyclic inhibitors
Autodock Vina 1.1.2
UCSF Chimera 1.13.1 (http://www.cgl.ucsf.edu/chimera/) with Vina interface plugin
PDBBind database 2018 (http://www.pdbbind.org.cn)
MS Excel
pH 7.4
The Pearson correlation was calculated between the top Vina docking score and experimental ln(Kd) for known macrocyclic inhibitors of human BACE-1.
The inhibitors were selected from the PDBbind database (2PH8, 3DV1, 4DPF, 2F3F, 2F3E, 4DPI, 4KE0). The final equation was as following:
ln(Kd) = 0.66*Vina score - 9.5; (r=0.85 after exclusion of one outlier).
The binding energy was calculated at 298K as (-R*T*ln(Kd))/4184
No