The fast pulling of ligand (FPL) method, which evaluates the relative ligand-protein binding affinity with low CPU usage and high accuracy, was applied for the first time to determine the affinity of beta-secretase 1 (BACE1) and its inhibitors using steered-molecular dynamics simulations. The total non-bonded interaction energy difference Delta E-total is a highly appropriate criterion to predict the relative BACE1-inhibitor binding affinity with strong correlation to experimental data (R = 0.92) and small deviation (delta E-totat = 7%). The van der Waals interaction and electrostatic interaction contribute 56% and 44% to the total non-bonded interaction energy between BACE1 and its inhibitors.(c) 2017 Published by Elsevier B.V.