Study on the Self-assembly of Diphenylalanine-based Nanostructures by Coarse-grained Molecular Dynamics Cong Guo and Guanghong Wei Physics Department, Fudan University, Shanghai, PRC Self-assembly plays a vital role in many biological systems, e. g. the formation of cell membranes. The assembly of diphenylalanine (FF, 苯丙氨酸二肽) peptides leads to the formation of kinds of nanostructures which are attracting increasing attention owing to their biocompatibility and good mechanical properties. FF-based nanostructures have potential application in drug delivery and templates for nanofabrication. But so far experimental techniques can’t give dynamic information at atomic-level and nanosecond time scale. There’s a lack of insight into the assembly process, protein-protein interaction, water-protein interaction and detail characteristics of nanostructures. Using coarse-grained model, long time computational simulations are complementary to available experimental data. Fig. 1 Radius of gyration evolves with time. vesicle Methods Protein and water Model: coarse-grained model (Martini V2.1 force field) Computational Methods: Molecular Dynamics Software: GROMACS V3.3.3 System: 600 peptides, 3 initial systems at 85 mg/ml, 120 mg/ml and 155 mg/ml Time: 600~1200 ns and ten simulations per Coarse-grained model Chemical structure of FF nanotube 0 ns 13.5 ns 19.2 ns Formation of vesicle 100 ns cx 85 ns 0 ns Formation of nanotube 33 ns 240 ns Radius of gyration (Fig.1) fluctuating around a constant after 200 ns indicates our simulations have reached equilibrium. Except vesicle and nanotube, bilayer and curved bilayer were also observed which are intermediate structures on the assembly way. Special Assembly Ways 66 ns 83 ns 170 ns 233 ns 0 ns Two vesicles fuse into nanotube Fig. 2 Number of water interacting with protein evolves with time Fig. 3 Left: Probability density of angles between aromatic rings. Right: Probability of dihedral angles Charged backbone terminals attracted each other and interact with water. Hydrophobic side chains are buried away from water, so water-water interaction is enhanced which is crucial to stabilize nanostructures. Nanotube has least contacts with water compared to vesicle and bilayer (Fig. 2 left). During the fusion of two vesicles, a decrease in free energy is achieved by decreasing protein-water interaction(Fig. 2 right) Sidechains lie at the same side of backbone (Fig. 3 right: a peak at 0°) and adopt T-shaped conformation (Fig. 3 left: anlges between 60- 120 degrees). Conclusion Using coarse-grained molecular dynamics we obtained dynamics insights into the assembly process and characteristics of FF-based nanostructures. Now we are studying the all-atom structures reconstructed from coarse-grained results with atomic details and test their stabilities. Reference: [1] Xuehai Yan, Junbai Li. Chem. Soc. Rev., 2010, 39, 1877–1890 [2] Junbai Li et al. Angew. Chem., Int. Ed., 2007, 46, 2431–2434 [3] Siewert-Jan Marrink et al. J. Chem. Theory and Comput., 2008，4, 819- 834 111 ns 306 ns 559 ns 600 ns Two vesicles fuse into elongated vesicle 0 ns