File Name : si_figure_1.tif Caption : figure 1. statistics of 2000 zdock results. residues in chain h of the fibril are shown in the left column (a)(c), and residues in chain i in the right column(b)(d). we mapped the number of counts to the cartoon structure; blue represents small number of counts and red represents large number of counts. File Name : si_figure_2.tif Caption : figure 2. (a) potentials of mean force (pmfs) for complex 5 obtained from 5 sets of umbrella sampling md simulations with different force constants and window simulation lengths. standard deviation is shown for each pmf profile. as window length increases, the pmf converges to a stable profile when the simulation time for each window is beyond 5 ns. (b) distance histograms of individual windows show excellent overlap for one of the umbrella sampling simulations (window length = 10 ns and k = 1000 kj/mol/nm2). File Name : si_figure_3.tif Caption : figure 3. potential of mean force (pmf) curves for top 9 zdock-predicted fibril-peptide complexes. File Name : si_figure_4.tif Caption : figure 4. occupancy of contact between a p62 residue and a residue in chain h (a) and chain i (b) of the fibril, respectively, during the md simulation of complex 5. red color indicates that the contact is formed for most of the time, and white means that no contact is observed. File Name : si_figure_5.tif Caption : figure 5. fraction of time that individual peptide residues involved in forming contact with fibril chain h (a) and chain i (b) during the md simulation of complex 5. the fibril residues involved in binding are mainly tyrosine and aspartic acid. red for aspartic acid, green for tyrosine and blue for all other residues. fraction of time that individual peptide residues involved in hydrogen bonding with chain h (c) and chain i (d). ser39, gln25, ser32 and tyr46 form more contacts with chain h than other residues, while gln31, lys27, gln28 and lys20 form more contacts with chain i. lysines in the peptide only form contacts with chain i of the fibril. as for hydrogen bonds, ser39, lys20 and gln31 are the main residues involved. File Name : si_figure_6.tif Caption : figure 6. sidechain length of lys20 and alignment angles formed between lys20 and asp50 and between lys20 and asp31 in the wt binding structure. File Name : si_figure_7.tif Caption : figure 7. time trajectories of the three geometric values for lys20 are shown during the pulling simulation. angle of lys20ca-lys20nz-asp31cg and d-directivity (ab), angle of lys20ca-lys20nz-asp50cg and d-directivity (cd), sidechain length and d-directivity (ef). File Name : si_figure_8.tif Caption : figure 8. percentage of time that a peptide residue is engaged in contact with chain h (left column) and chain i (right column) of the fibril as a function of separation distance distances during the umbrella sampling simulation of complex 5. (a) for lys13, lys20, gln25, lys27, gln28. (b) for gln31, ser32, ser36, ser39, tyr46. if the percentage is higher than 100%, it means that the specific residue forms more than one contact with the fibril. File Name : si_figure_9.tif Caption : figure 9. occupancy of contact between a p62 residue and a fibril residue in chain h (the left column) and chain i (the right column) at various separation distances during the umbrella sampling simulation of complex 5. the distance for the top panel is 2.11 nm (a,b), for the middle panel is 2.9 nm (c,d), and for the bottom panel is 3.78 nm (e) and 4.14 nm (f). (a) and (b) indicate bound complex, and (e) and (f) indicate dissociated complex. red color indicates that a contact exists for most of the time during the simulation, while white color means that no contact is formed. File Name : si_figure_10.tif Caption : figure 10. histogram of d-directivity for lys13, lys20, lys27 and gln31 at various separation distances during the umbrella sampling simulation of complex 5. the general trend is obvious. at far distances (~5.2nm), the distribution of d-directivity values is relatively even and broad. as the distance decreases to around 3.3 nm, the distributions of d-directivity for lys20, lys27 and gln31 show sharper peaks, with the peak position approximately equal to the length of the respective residue’s sidechain. at near distances, the distribution of d-directivity value occupies between 0.2nm and 0.3nm, if the residue could form contact with the fibril. a peak starts to form and moves from the right to the left as the fibril-peptide distance decreases. File Name : si_figure_11.tif Caption : figure 11. chord diagrams of contact connections of the peptides (including the original peptide p62 and five p62 mutants) and the fibril chain h or chain i during the md simulations. peptide is shown in green, fibril chain h in dimgray, and chain i in lightgray. the color bar shows the fraction of time for each contact connection. chord diagrams were plotted by using mne-python package. File Name : si_figure_12.tif Caption : figure 12. chord diagram of contact connections of the peptides (including the original peptide p62 and five p62 mutants) and the fibril chain h or chain i during the md simulations. peptide is shown in green, fibril chain h in dimgray, and chain i in lightgray. the color bar shows the fraction of time for each contact connection. File Name : si_figure_13.tif Caption : figure 13. the final structure of complex 5 (a), complex 37 (b) and complex 49 (c) generated by zdock and refined by md simulation are shown in a cartoon representation. p62 is shown in green (middle), chain h in gray (left) and chain i in white (right). lysines in the peptide and aspartic acids in the fibril are shown in licorice colored by residue type (blue for positively charged and red for negatively charged). File Name : si_figure_14.tif Caption : figure 14. representative binding intermediate structures and d-directivity values as a function of time during the pulling (smd) simulations of mutations k27a (ace) and q31a (bdf). peptide is shown in green, fibril chain h in gray, and chain i in white. residues involved in contact are represented in licorice and colored by residue type (red for negatively charged residues, blue for positively charged residues, green for polar residues, and white for hydrophobic residues). the time trajectories of the d-directivity (green), the minimum distance between cα of the residue and the fibril (red), and the minimum distance between the sidechain atoms of the residue and the fibril (blue), are shown for lys20 (cd), gln31(e) and lys27 (f) during the simulations.