1. 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, 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 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,
111 ns
306 ns
559 ns
600 ns
Two vesicles fuse into elongated vesicle
0 ns