Docking and molecular dynamics simulations of the Fyn-SH3 domain with free and phospholipid bilayer-associated 18.5-kDa myelin basic protein (MBP)Insights into a noncanonical and fuzzy interaction

作者：Bessonov Kyrylo; Vassall Kenrick A; Harauz George

来源：Proteins: Structure, Function, and Genetics , 2017, 85(7): 1336-1350.

DOI：10.1002/prot.25295

• amphipathic -helix
• poly-proline type II (PPII)
• Fyn-SH3
• intrinsically disordered protein (IDP)
• myelin basic protein (MBP)
• molecular dynamics (MD) simulations
• molecular recognition fragment (MoRF)
• GROMACS

The molecular details of the association between the human Fyn-SH3 domain, and the fragment of 18.5-kDa myelin basic protein (MBP) spanning residues S38-S107 (denoted as x2-peptide, murine sequence numbering), were studied in silico via docking and molecular dynamics over 50-ns trajectories. The results show that interaction between the two proteins is energetically favorable and heavily dependent on the MBP proline-rich region (P93-P98) in both aqueous and membrane environments. In aqueous conditions, the x2-peptide/Fyn-SH3 complex adopts a sandwich"-like structure. In the membrane context, the x2-peptide interacts with the Fyn-SH3 domain via the proline-rich region and the -sheets of Fyn-SH3, with the latter wrapping around the proline-rich region in a form of a clip. Moreover, the simulations corroborate prior experimental evidence of the importance of upstream segments beyond the canonical SH3-ligand. This study thus provides a more-detailed glimpse into the context-dependent interaction dynamics and importance of the -sheets in Fyn-SH3 and proline-rich region of MBP. Proteins 2017; 85:1336-1350.

• 出版日期2017-7