Paper Citing NAMD - Abstract
Vargas, Diego A.; Zaman, Muhammad H.
Serine at Phosphorylation Site Regulates the Mechanical and Structural Behavior of Fascin
CELLULAR AND MOLECULAR BIOENGINEERING, 2:504-513, DEC 2009
The mechanical behavior of fascin was examined using steered molecular dynamics. Constant velocity pulling was performed on the beta-chain molecule of human wild type fascin and the mutants arising from a single amino acid substitution. Residue 39 was substituted because it is crucial to fascin binding of actin in filopodia formation. Based on empirical observations, duration of the simulation was chosen to be 430 ps. Velocity of pulling was 0.5 /ps. In each simulation force acting on the molecule, total extension of the molecule, and evolution of the secondary structure were monitored. Different unfolding of residues 8-48 during the first 215 ps is observed in the trajectories for the different molecules. Ramachandran plots were used for additional analysis of the behavior of a penta-peptide region centered on residue 39. The resulting observations show that mutation of residue 39 causes a change in the mechanical behavior of the protein: The mutant with alanine in position 39 more closely resembles that of the wild type molecule in stability, while the mutant with glutamic acid in this position is more unstable. This supports the hypothesis that the mechanical behavior of the protein upon phosphorylation or dephosphorylation of residue 39 (forms simulated by the glutamic acid and alanine mutants respectively) is responsible for the regulation of binding cycles between fascin and actin and therefore crucial to cell sensing and movement.
