Molecular Dynamics Simulation of Self-Assembly Processes of Diphenylalanine Peptide Nanotubes and Determination of Their Chirality

Abstract

In this work, we further developed a new approach for modeling the processes of the self-assembly of complex molecular nanostructures using molecular dynamics methods; in particular, using a molecular dynamics manipulator. Previously, this approach was considered using the example of the self-assembly of a phenylalanine helical nanotube. Now, a new application of the algorithm has been developed for implementing a similar molecular dynamic self-assembly into helical structures of peptide nanotubes (PNTs) based on other peptide molecules-namely diphenylalanine (FF) molecules of different chirality L-FF and D-FF. In this work, helical nanotubes were assembled from linear sequences of FF molecules with these initially different chiralities. The chirality of the obtained nanotubes was calculated by various methods, including calculation by dipole moments. In addition, a statistical analysis of the results obtained was performed. A comparative analysis of the structures of nanotubes was also performed using the method of visual differential analysis. It was found that FF PNTs obtained by the MD self-assembly method form helical nanotubes of different chirality. The regimes that form nanotubes of right chirality D from initial L-FF dipeptides and nanotubes of left chirality L from D-FF dipeptides are revealed. This corresponds to the law of changing the sign of the chirality of molecular helical structures as the level of their hierarchical organization becomes more complicated.

Keywords: chirality; controlled molecular dynamics; diphenylalanine; dipole moment; molecular dynamics method; nanotubes; self-assembly of nanostructures; visual differential analysis.

Figure 1

Initial linear structure of 24 dipeptides: (a) Poly(L-FF)₂₄; (b) Poly(D-FF)₂₄. Fragments of the 7 dipeptides are shown. Original models are constructed in the HyperChem program [34].

Figure 2

Final results after MDS self-assembly and helix structure formation: (a) on the left, a left-handed chiral L-form based on right-handed molecules (D-FF)₂₄; (b) right-handed chiral D-form based on left-handed molecules (L-FF)₂₄. Projection along the axis of the nanotube in the RasMol image—pdb file, using PyMOL [43].

Figure 3

Scheme for determining the vectors of the helical structure from the references [13,44]. Cα-atoms for calculating the chirality from the mixed vector product [13].

Figure 4

Images of helix coils of helical structures obtained from experimental data from [13,14]: (a) for a helix coil based on L-FF with chirality D; (b) for a helix coil based on D-FF with chirality L.

Figure 5

Images of the main part of the helical structure of a nanotube obtained by MDS self-assembly based on L-FF dipeptides, which has a right-handed chirality D: (a) view in the cross-sectional plane of a nanotube lying perpendicular to the OZ axis of the tube; (b) side view of the nanotube coils along the OX axis; (c) side view of the nanotube coils along the OY axis. The numbers in the figure mean the numbers of the coordinate axes 1-X, 2-Y, 3-Z. This structure consists of 19 FF dipeptides and is obtained on the basis of MDS-assembled nanotube No. 31 (in Table 1) formed from 24 FF dipeptides. (Here, 5 dipeptides were removed, forming poorly ordered regions at the ends of this helical structure, and its main part was left).

Figure 6

Images of the main part of the helical structure of a nanotube obtained by MD self-assembly based on D-FF dipeptides, which has a left chirality L: (a) view in the cross-sectional plane of a nanotube lying perpendicular to the OZ axis of the tube; (b) side view of the nanotube coils along the OX axis; (c) side view of the nanotube coils along the OY axis. The numbers in the figure mean the numbers of the coordinate axes 1-X, 2-Y, 3-Z. This structure consists of 19 FF dipeptides and is obtained on the basis of nanotube No. 25 (in Table 1) formed from 24 FF dipeptides. (Here, 5 dipeptides were removed, forming poorly ordered regions at the ends of this helical structure, and its main part was left).