Book of Abstracts: Albany 2011

category image Albany 2011
Conversation 17
June 14-18 2011
©Adenine Press (2010)

Computational Microscopy

Biomolecular modeling, taking advantage of ever increasing computer power, has dramatically improved in accuracy as well as in time and size scale covered. For example, low resolution single molecule force measurements are imaged at atomic resolution through steered molecular dynamics simulations; crystallography and electron microscopy data, combined through molecular dynamics flexible fitting calculations, are interpreted through atomic level structures of functional intermediates of large cellular machines; simulations at multiple length scales show movies of peripheral membrane proteins sculpting cellular membranes. The lecture will illustrate for three examples atomic resolution images and movies provided by means of biomolecular modeling as a result of new simulation concepts, algorithms, and technology.

A computational-experimental collaboration (with H. Gaub, Munich) discovered a possibly fundamental epigenetic mechanism of methylated DNA. Highly sampled chip-based stretching of double stranded DNA combined with simulation revealed that strand separation mechanics is strongly affected by epigenetic modification of DNA. The study, involvingd long time scale and large size simulations, resolved and explained the observed effect of DNA methylation.

Atomic resolution crystallographic structures and electron microscopy density maps at better than 10 Angstrom resolution (from R. Beckmann, Munich) were combined in a computational analysis employing a new simulation method, molecular dynamics flexible fitting, to construct an atomic resolution structure of a ribosome seen in the process of threading a nascent protein through a translocon into a biological membrane. The simulations revealed also in great detail the interaction between nascent protein and ribosomal exit channel as well as interaction with the translocon, for example the binding of the signaling element to the translocon.

The shape of cellular membranes can be induced by peripheral proteins for example N-BAR and F-BAR domains. The latter proteins have been observed in vitro to form tubular membranes from vesicles and a similar behavior has been seen in simulations. Employing a combination of coarse-grained and all atom molecular dynamics simulations, calculations offer movies revealing how the peripheral proteins, in forming regular lattices as observed by electron microscopy (Unger, Yale U.), bend flat membranes into tubes, the latter remaining stable after removal of protein. The simulations shed light on the protein - lipid interactions responsible for membrane bending.

Klaus Schulten

Department of Physics
University of Illinois at Urbana-Champaign
Urbana, IL 61801 USA