Molecular dynamics study of amyloid formation of two Abl-SH3 domain peptides.
Molecular dynamics (MD) simulations were carried out for two-strand and ten-strand beta-sheets constructed from two peptides corresponding to the diverging turn of two homologous Abl-SH3 domains, DLSFMKGE (MK; from Drosophila) and DLSFKKGE (KK; from man), in explicit water at the temperatures of 30, 170/190 and 300 K. It was found that the 2 x MK beta-sheet is more stable than the 2 x KK beta-sheet, and that the 10 x MK beta-sheet is more stable than the 10 x KK beta-sheet; this suggests that the MK systems are fibril-creating and the KK systems are not. These results might explain why most SH3 domains possess two conserved basic residues at the diverging turn, which may act as gatekeepers in order to avoid aggregation.
Liepina
Inta
I
Latvian Institute of Organic Synthesis, Riga, LV1006, Latvia. inta@osi.lv
Ventura
Salvador
S
Czaplewski
Cezary
C
Liwo
Adam
A
D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D003198:Computer Simulation; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010446:Peptide Fragments / Q000737:chemistry*; D017433:Protein Structure, Secondary; D013696:Temperature; D013816:Thermodynamics; D014867:Water; D018909:src Homology Domains
D000682:Amyloid; D010446:Peptide Fragments; D014867:Water