1 research outputs found
Can We Execute Stable Microsecond-Scale Atomistic Simulations of Protein–RNA Complexes?
We
report over 30 ÎĽs of unrestrained molecular dynamics simulations
of six protein–RNA complexes in explicit solvent. We utilize
the AMBER ff99bsc0χ<sub>OL3</sub> RNA force field combined with
the ff99SB protein force field and its more recent ff12SB version
with reparametrized side-chain dihedrals. The simulations show variable
behavior, ranging from systems that are essentially stable to systems
with progressive deviations from the experimental structure, which
we could not stabilize anywhere close to the starting experimental
structure. For some systems, microsecond-scale simulations are necessary
to achieve stabilization after initial sizable structural perturbations.
The results show that simulations of protein–RNA complexes
are challenging and every system should be treated individually. The
simulations are affected by numerous factors, including properties
of the starting structures (the initially high force field potential
energy, resolution limits, conformational averaging, crystal packing,
etc.), force field imbalances, and real flexibility of the studied
systems. These factors, and thus the simulation behavior, differ from
system to system. The structural stability of simulated systems does
not correlate with the size of buried interaction surface or experimentally
determined binding affinities but reflects the type of protein–RNA
recognition. Protein–RNA interfaces involving shape-specific
recognition of RNA are more stable than those relying on sequence-specific
RNA recognition. The differences between the protein force fields
are considerably smaller than the uncertainties caused by sampling
and starting structures. The ff12SB improves description of the tyrosine
side-chain group, which eliminates some problems associated with tyrosine
dynamics