The multi-scale simulation methodology employed by the Voth Group relies on recasting the original, atomistically detailed system in new, renormalized and/or coarse-grained representations, and then bridging the different representations via a systematic coupling methodology. At the atomistic-level, molecular dynamics (MD) and non-equilibrium molecular dynamics (NEMD) are employed. At the continuum-level novel modeling techniques capable of simulating large membrane structures such as giant unilamellar vesicles (GUV's) have been developed. Then, at the mesoscale, a new and very significant effort has been invested in developing mesoscopic models for membranes (and other biological assemblies such as spectrin and actin) along with the surrounding solvent, in a manner that is consistent with our overall multi-scale simulation methodology.
The implementation of a multi-scale simulation methodology involves passing selected information (in the form of material properties) back and forth between different spatial/temporal representations of the system. The theoretical foundations come from established theoretical frameworks related to field theoretical models for complex systems. Within this framework, it is formally possible to transform an atomistic system into a new effective field theory-based representation. In mapping an atomistic-level system (i.e., a bilayer, solvent, with perhaps an embedded protein) onto a field theory, cumulative averaged atomistic-level interactions are "projected" onto a new "smoothed out" system: the atomistic-level detail is formally mapped onto a field theory.
An additional component within the overall multi-scale scheme is the so-called coarse-grained MD (CG MD) methodology in which all-atom representations of biomolecules are mapped into simpler "quasi-molecular" systems having fewer (course grained) groups and effective interactions between those groups. CG MD provides a valuable bridge between all-atom representations and a more abstract field-theoretic picture at larger mesoscopic length- and time-scales. In order to more systematically bridge the atomistic and mesoscopic spatial/temporal regimes with such an approach, a new CG MD strategy has been recently developed in the Voth Group that directly employs underlying atomistic-scale MD forces in the construction of CG MD models. This new algorithm is called multi-scale coarse-graining (MS CG).
In the following subsections, specific applications of our multi-scale modeling approach are discussed: Next ⇒
