Molecular
view of a coarse-grained model based on the original structure of M13 major
coat proteins Credit: SUTD.
Atomistic
simulations are a powerful tool to study the movement and interactions of atoms
and molecules. In many biological processes, large-scale effects, for example,
assembly of large viruses to nanoparticles are important. The assembly
processes of these large viruses are of fundamental importance to the design of
many devices and viral protein-targeted therapeutics. However, the time and
length scale of these assembly processes are usually too large for simulations
at molecular resolution.
Moreover,
even though an increase in computing power allows for more complex and longer
simulations, virus structures, such as M13, are still beyond reach. That is why
a research group from the Singapore University of Technology and Design (SUTD)
and the Massachusetts Institute of Technology (MIT) has developed a procedure
that links large-scale assembly processes to molecular simulations. Assistant
Prof Desmond Loke from SUTD's Science, Mathematics and Technology cluster said,
"For the simulation of M13, we started with different sets of force fields.
Suitable force fields were chosen and they were used as the inputs for a
molecule dynamics simulations with the coarse-grain model designed to capture
key pattern of the assembly process."
"While
we know that M13-based manufacturing can be fundamentally driven by
nanoparticle-peptide interactions, which may also be a key principle behind
M13-type bioengineering, we have little knowledge of how repeated patterns of
short-end-peptides on a M13 surface are actually involved in these
interactions. To study this, we ideally have to include a full structure of the
viral coat-protein, which is a difficult task for current state-of-the-art
molecular dynamics simulations," adds Dr. Lunna Li, first author of the
article.
The
procedure allows users to add different types of nanoparticles to a solution,
at a realistic level. Inspired by this procedure, Assistant Professor Loke and
his colleagues were able to simulate a large-scale virus with nanoparticles and
inside a solution for fifty nanoseconds.
Dr. Li
said, "The virus structure and solution contain about 700,000 atoms
overall." Considering the shape and size of the features, the complexity
of this simulation can be larger than any simulation performed previously.
"A
simulation performed in microseconds would have been possible if a smaller M13
model was used, but it can be worthwhile to reduce the time to actually observe
how the full structure may influence the assembly between the M13 and
nanoparticles," explained Assistant Prof Loke.