Construction of an implicit membrane environment for the lattice Monte Carlo simulation of transmembrane protein

Abstract

Due to the complexity of biological membrane, computer simulation of transmembrane protein's folding is challenging. In this paper, an implicit biological membrane environment has been constructed in lattice space, in which the lipid chains and water molecules were represented by the unoccupied lattice sites. The biological membrane was characterized with three features: stronger hydrogen bonding interaction, membrane lateral pressure, and lipophobicity index for the amino acid residues. In addition to the hydrocarbon core spanning region and the water solution, the lipid interface has also been represented in this implicit membrane environment, which was proved to be effective for the transmembrane protein's folding. The associated Monte Carlo simulations have been performed for SARS-CoV E protein and M2 protein segment (residues 18-60) of influenza A virus. It was found that the coil-helix transition of the transmembrane segment occurred earlier than the coil-globule transition of the two terminal domains. The folding process and final orientation of the amphipathic helical block in water solution are obviously influenced by its corresponding hydrophobicity/lipophobicity. Therefore, this implicit membrane environment, though in lattice space, can make an elaborate balance between different driving forces for the membrane protein's folding, thus offering a potential means for the simulation of transmembrane protein oligomers in feasible time.

Fig. 1

Sketch map for the biological membrane environment and some typical snapshots of SARS-CoV E protein during the associated folding process. Gray zone and blue zone represent the membrane's hydrocarbon core and lipid interface respectively. The polypeptide segments in hydrocarbon core and lipid interface and water solution are colored in green, blue, and gray correspondingly. The two ends of the helical segment are labeled in red color. (A) 1/T^⁎ = 0; (B) 1/T^⁎ = 0.64; (C) 1/T^⁎ = 1.28; (D) 1/T^⁎ = 2.08; (E) 1/T^⁎ = 8.16; (F) 1/T^⁎ = 8.16.

Fig. 2

Reduced specific heat (c^⁎_V) and chain energy (E) as functions of inversed temperature (1/T^⁎) for SARS-CoV E protein. The dashed lines indicate the peak positions of specific heat corresponding to the coil–helix transition point and the coil–globule transition point. Error bars come from the standard deviations of all trajectories.

Fig. 3

Number of residues (n_r) in specific regions of the membrane as functions of inversed temperature (1/T^⁎) for SARS-CoV E protein. The dashed line indicates the peak position of specific heat corresponding to the coil–helix transition point.

Fig. 4

Mean square radius of gyration <S²> as a function of inversed temperature (1/T^⁎) for SARS-CoV E protein's three chain segments.

Fig. 5

Comparison of the length of helix block (L_h), the number of residues (n_r) in the cytoplasmic side and the mean square radius of gyration <S²>₃₅₋₇₆ for SARS-CoV E protein's segment between the cases with and without membrane's lipid interface.

Fig. 6

Typical snapshots of the M2(18–60) segment during the folding process. Gray zone and blue zone represent the membrane's hydrocarbon core and lipid interface respectively. The polypeptide segments in hydrocarbon core and lipid interface and water solution are colored in green, blue, and gray correspondingly. The two ends of the helical segment are labeled in red color. (A) 1/T^⁎ = 0; (B) 1/T^⁎ = 0.48; (C) 1/T^⁎ = 1.6; (D) 1/T^⁎ = 2.56; (E) 1/T^⁎ = 7.36; (F) 1/T^⁎ = 9.6; (G) 1/T^⁎ = 9.6. (F) and (G) are the same conformation but from different angles of view.

Fig. 7

Helical ratio (θ) as a function of inversed temperature (1/T^⁎) for the M2(18–60) segment's two helices.

Fig. 8

Tilt angle (ω) as a function of inversed temperature (1/T^⁎) for the M2(18–60) segment's two helices.