Leonardo G. Trabuco, Eduard Schreiner, James Gumbart, Jen Hsin, Elizabeth
Villa, and Klaus Schulten.
Applications of the molecular dynamics flexible fitting method.
Journal of Structural Biology, 173:420-427, 2011.
(PMC: 3032011)
TRAB2011
In recent years, cryo-electron microscopy (cryo-EM) has established
itself as a key method in structural biology, permitting the
structural characterization of large biomolecular complexes in various
functional states. The data obtained through single-particle cryo-EM has recently seen a
leap in resolution thanks to landmark
advances in experimental and computational techniques, resulting in
sub-nanometer resolution structures being obtained routinely. The remaining gap
between these data and revealing the mechanisms of
molecular function can be closed through hybrid modeling tools that
incorporate known atomic structures into the cryo-EM data. One such tool, molecular
dynamics flexible fitting (MDFF), uses
molecular dynamics simulations to combine structures from X-ray
crystallography with cryo-EM density maps to derive atomic models of
large biomolecular complexes. The structures furnished by MDFF can be used
subsequently in computational investigations aimed at revealing the dynamics
of the complexes under study. In the present work, recent applications of MDFF are
presented, including the interpretation of cryo-EM data of the ribosome at different
stages of translation and the structure of a membrane-curvature-inducing photosynthetic
complex.
