Alexander J. Bryer, Jodi A. Hadden-Perilla, John E. Stone, and Juan R. Perilla.
High-performance analysis of biomolecular containers to measure
small-molecule transport, transbilayer lipid diffusion, and protein cavities.
Journal of Chemical Information and Modeling, 59:4328-4338,
2019.
(PMC: PMC6817393)
BRYE2019-JS
Compartmentalization is a central theme in biology. Cells are composed of
numerous membrane-enclosed structures, evolved to facilitate specific
biochemical processes; viruses act as containers of genetic material, optimized
to
drive infection. Molecular dynamics simulations provide a mechanism to study
biomolecular containers and the influence they exert on their environments;
however, trajectory analysis software generally lacks knowledge of container
interior versus exterior. Further, many relevant container analyses involve large-
scale particle tracking endeavors, which may become computationally
prohibitive
with increasing system size. Here, a novel method based on 3-D ray casting is
presented, which rapidly classifies the space surrounding biomolecular
containers of arbitrary shape, enabling fast determination of the identities and
counts of particles (e.g., solvent molecules) found inside and outside. The
method is broadly applicable to the study of containers and enables high-
performance characterization of properties such as solvent density, small-
molecule transport, transbilayer lipid diffusion, and topology of protein cavities.
The method is implemented in VMD, a widely used simulation analysis tool that
supports personal computers, clouds, and parallel supercomputers, including
ORNL’s Summit and Titan and NCSA’s Blue Waters, where the method can be
employed to efficiently analyze trajectories encompassing millions of particles.
The ability to rapidly characterize the spatial relationships of particles relative
to
a biomolecular container over many trajectory frames, irrespective of large
particle counts, enables analysis of containers on a scale that was previously
unfeasible, at a level of accuracy that was previously unattainable.