Figure 5.

Pep-GaMD simulations have captured repetitive dissociation and binding of three model peptides to the SH3 domains: (A-C) X-ray structures of the SH3 domains bound by peptides (A) “PAMPAR” (PDB: 1SSH), (B) “PPPALPPKK” (PDB: 1CKA) and (C) “PPPVPPRR” (PDB: 1CKB). The SH3 domains and peptides are shown in green and magenta cartoon, respectively. Key protein residues Asp19 and Trp40 in the 1SSH structure and Asp150 and Trp169 in the 1CKA and 1CKB structures, and peptide residues Arg10 in the 1SSH structure, Lys8 in the 1CKA structure and Arg7 in the 1CKB structure are highlighted in sticks. The “N” and “C” labels denote the N-terminus and C-terminus of the peptides. (D–F) time courses of peptide backbone RMSDs relative to X-ray structures with the protein aligned calculated from three independent 1 μs Pep-GaMD simulations of the (D) 1SSH, (E) 1CKA and (F) 1CKB structures. (G–I) The corresponding PMF profiles of the peptide backbone RMSDs averaged over three Pep-GaMD simulations of the (G) 1SSH, (H) 1CKA and (I) 1CKB structures. Error bars are standard deviations of the free energy values calculated from three Pep-GaMD simulations. Reprinted from “Jinan Wang, Yinglong Miao, J Chem Phys 2020, 153:154109”, with the permission of AIP Publishing.