Molecular Dynamics Simulation Study of the Self-Assembly of Phenylalanine Peptide Nanotubes

Abstract

In this paper, we propose and use a new approach for a relatively simple technique for conducting MD simulation (MDS) of various molecular nanostructures, determining the trajectory of the MD run and forming the final structure using external force actions. A molecular dynamics manipulator (MD manipulator) is a controlled MDS type. As an example, the applicability of the developed algorithm for assembling peptide nanotubes (PNT) from linear phenylalanine (F or Phe) chains of different chirality is presented. The most adequate regimes for the formation of nanotubes of right chirality D from the initial L-F and nanotubes of left chirality L of their initial dipeptides D-F modes were determined. We use the method of a mixed (vector-scalar) product of the vectors of the sequence of dipole moments of phenylalanine molecules located along the nanotube helix to calculate the magnitude and sign of chirality of self-assembled helical phenylalanine nanotubes, which shows the validity of the proposed approach. As result, all data obtained correspond to the regularity of the chirality sign change of the molecular structures with a hierarchical complication of their organization.

Keywords: MD manipulator; chirality; controlled molecular dynamics; molecular dynamics method; nanotubes; phenylalanine; self-assembly of nanostructures.

Figure 1

The initial structure of Poly(Phe)₄₈. Models were constructed in the HyperChem program [32]: (a) L-Phe (L-F) β-sheet; (b) D-Phe (D-F) β-sheet. Reprinted with permission from [21].

Figure 2

Additional force impacts: (a) “diametric stretch marks; (b) “helix pitch”. Reprinted with permission from [21].

Figure 3

Final results: (a) after giving a helix-like shape; (b) after adding additional diametric springs, pulling back amino acid residues. Reprinted with permission from [21].

Figure 4

Phe nanotube of 100 amino acid residues. Reprinted with permission from [21].

Figure 5

The final results obtained by MDS and self-assembly of phenylalanine helix-like structures: (a) a right-handed chiral D-PNT nanotube based on an MD assembly of 48 phenylalanine molecules L-F48 of the initial left-handed chirality L-F or L-Phe (corresponding pdb file L-F48.pdb); (b) left-handed chiral nanotube L-PNT based on MD assembly 48 phenylalanine molecules D-F48 of the initial right-handed chirality D-F or D-Phe (corresponding pdb file D-F48.pdb). Reprinted with permission from [54].

Figure 6

Shape of phenylalanine molecules and total dipole moment D_t = D orientation: (a) for the left-handed chiral isomer L-F (or L-Phe); (b) for the right-handed chiral isomer D-F (or D-Phe).

Figure 7

The obtained results of MDS and self-assembly of phenylalanine helix-like PNTs, transferred into HyperChem workspace (in Z-projection): (a) L-F48; (b) D-F48 (Reprinted with permission from [54]).

Figure 8

Images of one coil selected and cut from the four coils of the PNT helix-like structures (in X-projection): (a) for a PNT coil based on L-F; (b) for a PNT coil based on D-F (Reprinted with permission from [54]).

Figure 9

Scheme of the selection procedure of each consequential phenylalanine F molecule (from 1 to 12) from one corresponding coil of PNT helix and calculation of its dipole moment D_i (for i = 1, 12) (in Z-projections): (a) for the D-PNT based on phenylalanine of left-handedness L-F; (b) the same for L-PNT based on right-handedness D-F, correspondingly. (Reprinted with permission from [54]).