In this lecture we present two model studies that seek to overcome, through multiiscale methods, size and time scale limitations in biomolecular modeling. The first system involves a complex between the lac repressor protein (LacI) and a DNA segment, the protein being described by all-atom molecular dynamics and the DNA forming a loop being modeled as a continuous elastic ribbon through the so-called Kirchhoff equations. The forces stemming from the looped DNA, enforced through binding to the protein, are included in the molecular dynamics simulations; the loop structure and the forces are continuously recomputed because the protein motion during the simulation shifts the DNA termini of the loop. The simulations reveal the structural dynamics of the LacI-DNA complex in unprecedented detail. The multiple domains of LacI exhibit remarkable structural stability during the simulation, moving much like rigid bodies. LacI is shown to absorb the strain from the looped DNA mainly through its mobile DNA-binding head groups. The second system involves a complex of lipoprotein and lipids. The lipids form a disk-like bilayer; the long alpha-helical lipoprotein surrounds the disk like a belt with its hydrophobic side towards the tails and the hydrophilic side towards solvent. In order to investigate the aggregation of the complex water, lipid, and protein were described by all-atom as well as coarse-grained models, the latter permitting long simulation times. First results of simulations capturing phases of the aggregation process will be presented at both the all-atom and coarse-grained level.
Klaus Schulten, Anton Arkhipov, Peter Fredolino, Amy Shih, and Elizabeth Villa
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