Folding
Molecular Dynamics Simulations Accurately
Predict the Effect of Mutations on the Stability and Structure of
a Vammin-Derived Peptide
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Abstract
Folding
molecular dynamics simulations amounting to a grand total
of 4 μs of simulation time were performed on two peptides (with
native and mutated sequences) derived from loop 3 of the vammin protein
and the results compared with the experimentally known peptide stabilities
and structures. The simulations faithfully and accurately reproduce
the major experimental findings and show that (a) the native peptide
is mostly disordered in solution, (b) the mutant peptide has a well-defined
and stable structure, and (c) the structure of the mutant is an irregular β-hairpin
with a non-glycine β-bulge, in excellent agreement with the
peptide’s known NMR structure. Additionally, the simulations
also predict the presence of a very small β-hairpin-like population
for the native peptide but surprisingly indicate that this population
is structurally more similar to the structure of the native peptide
as observed in the vammin protein than to the NMR structure of the
isolated mutant peptide. We conclude that, at least for the given
system, force field, and simulation protocol, folding molecular dynamics
simulations appear to be successful in reproducing the experimentally
accessible physical reality to a satisfactory level of detail and
accuracy