Molecular dynamics of CBD3 peptide
We modeled the CBD3 peptide based on the X-ray diffraction structure of CRMP2 (PDB: 5MKV) (Zheng et al., 2018). Three independent molecular dynamics simulations (MDS) of both the CBD3 by itself and conjugated with a blood-brain barrier-permeable peptide TAT-CBD3 were run with pmemd.cuda (Case et al., 2018; Götz, Williamson, Xu, Poole, Le Grand & Walker, 2012; Salomon-Ferrer, Götz, Poole, Le Grand & Walker, 2013) from AMBER18 using AMBER ff14SB force field (Maier, Martinez, Kasavajhala, Wickstrom, Hauser & Simmerling, 2015). We used tLeap binary (AMBER18) for solvating the peptides in an octahedral TIP3P water box with a 15 Å distance from structure surface to the box edges, and closeness parameter of 0.75 Å. The neutralized system was solvated in a solution of 150 mM NaCl. H-bonds were constrained using SHAKE algorithm and integration time-step at 2 fs. Simulations were carried out equilibrating the system for 1 ns at NPT using Berstein barostat to keep constant pressure at 1 atm at 300K, followed by 300 ns NPT production at 300 K. The first 60 ns of each MDS were discarded as equilibration time.