In our lab, we are working to model biological systems in order to design and synthesize high performance biomaterials. Recently, we have investigated the mechanisms by which the high- aspect ratio and unique surface chemistry of M13 bacteriophage can give rise to increasingly complex, hierarchically ordered, bundled phage structures with a wide range of material applications. A molecular dynamic simulation of the 3-D structure of a 20-nm section of wild type (WT) and mutant phage types were developed based on WT phage crystal structure and ab initio calculations. Simulations of these phage were then used to examine repulsive and attractive forces of the particles in solution. Examination of contact interactions between two WT phage indicated the phage were maximally attracted to each other in a head to tail orientation. A mutant phage (4E) with a higher negative surface charge relative to WT phage also preferentially ordered head to tail in solution. In contrast, a mutant phage (CLP8) with a net positive surface charge had minimal repulsion in a 90° orientation. Understanding the self-assembly process through molecular dynamic simulations and decomposition of fundamental forces driving inter- and intra-strand interactions has provided a qualitative assessment of mechanisms that lead to hierarchical phage bundle structures. Results from simulation agree with experimentally observed patterns from self-assembly. We anticipate using this system to further investigate development of hierarchical structures not only from biological molecules but also from synthetic materials. Simulation methodology to generate force/distance curves. Pulling two units apart with MD.

Simulation unit model. Cylindrical unit cell of a MD simulated phage particle. A Side view of the unit model with 20 nm length scale B. Top view of the unit model with 6 nm length scale. C. Unit model of the three phage particles, CLP8, WT and 4E. Color corresponds to charge with blue as negative white as neutral and red as positive charge at simulated pH.

Force and Energy versus distance curves for two interacting phage simulated phage. Top panel displays the head to head configuration, bottom panel displays the head to tail configuration. 4E (blue triangles), WT (black squares) and CLP8 (red circles).

Force diagram between two phage particles at various rotational configurations. 4E (green squares), WT (blue circles) and CLP8 (red circles, on the right).