Exploring the Binding Mechanism between Human Profilin (PFN1) and Polyproline-10 through Binding Mode Screening

Leili Zhang; David R. Bell; Binquan Luan; Ruhong Zhou

To further observe what contributes to the RMSDs, we plotted the interfacial residue frequency in Figure S4 , with the initial occurrence frequency (0-50 ns) shown in Figure S4A , and final frequency (200-400 ns) shown in Figure S4B . The binding modes that feature major interfacial residue shifts are mode2, mode3, mode6, mode7 and mode8, mainly from Category I and Category II binding modes. More specifically, mode2 and mode8 in Category I deviate from the original hydrophobic interfacial binding, with mode2 transitioning to Category III and mode8 transitioning to Category IV, respectively. Even the relatively stable binding mode in Category I (mode1) shows a slight increase in the C-terminal region, which is the signature binding site of the co-crystal structure (Category IV). The mixed hydrophobic/hydrophilic binding interface Category II is also not very stable, with mode3 moving towards a hybrid Category II and Category III binding mode, and mode6 moving towards Category IV binding mode. Overall, all binding modes from Category I (mode1, mode2, mode8) and Category II (mode3, mode6, mode10) have tendencies to shift towards Category III and Category IV, which clearly indicates that MD simulations prefer the mixed hydrophobic/hydrophilic binding interfaces for P10. This All rights reserved. No reuse allowed without permission.