Molecular Dynamics Simulations of the E1/E2 Transmembrane Domain of the Semliki Forest Virus

Abstract

Transmembrane (TM) helix-helix interactions are important for virus budding and fusion. We have developed a simulation strategy that reveals the main features of the helical packing between the TM domains of the two glycoproteins E1 and E2 of the alpha-virus Semliki Forest virus and that can be extrapolated to sketch TM helical packing in other alpha-viruses. Molecular dynamics simulations were performed in wild-type and mutant peptides, both isolated and forming E1/E2 complexes. The simulations revealed that the isolated wild-type E1 peptide formed a more flexible helix than the rest of peptides and that the wild-type E1/E2 complex consists of two helices that intimately pack their N-terminals. The residues located at the interhelical interface displayed the typical motif of the left-handed coiled-coils. These were small and medium residues as Gly, Ala, Ser, and Leu, which also had the possibility to form interhelical Calpha-H...O hydrogen bonds. Results from the mutant complexes suggested that correct packing is a compromise between these residues at both E1 and E2 interhelical interfaces. This compromise allowed prediction of E1-E2 contact residues in the TM spanning domain of other alphaviruses even though the sequence identity of E2 peptides is low in this domain.

Effect of Urea on Peptide Conformation in Water: Molecular Dynamics and Experimental Characterization

“…However, in analogy to the helix-coil theory formalism of Rohl and Doig for conversion between 3 10 /a-helical segments (77), it could be possible that transitions between ato p-helical hydrogen bonds or vice versa will have a low penalty allowing such transitions. Even though p-helical formation has been observed in different MD simulations (78)(79)(80)(81)(82), it has been suggested that this is a force field artifact (83); in our simulations p-helix formation is mainly related to peptide instability, and in the case where the peptide is highly stable (Cpep 1 simulation in water at 277 K) p-helical hydrogen bonds were rarely found (Fig. 2).…”

Infectivity variation and genetic diversity among strains of Western equine encephalitis virus

“…Much of the available information on the molecular details of the structure and the pathogenesis of the alphaviruses has come from extensive studies with two members, SINV and Semliki Forest virus (SFV) (Atkins et al, 1999;Caballero-Herrera & Nilsson, 2003;Davis et al, 1986;Gibbons et al, 2004;Lustig et al, 1988;Olmsted et al, 1984;Polo & Johnston, 1991;Polo et al, 1988;Tuittila & Hinkkanen, 2003). Relatively little is known about the other alphaviruses, particularly WEEV.…”

A Molecular Dynamics Study of the Formation, Stability, and Oligomerization State of Two Designed Coiled Coils: Possibilities and Limitations

“…To date most of the MD simulations of coiled coils reported in the literature have been performed in vacuum (37)(38)(39), with specific constraints in the simulations (40) or using simplistic models (41). There have also been some studies of a-helical bundles in lipid bilayers (42,43), and Gorfe et al (32) carried out MD simulations in coiled coil systems in explicit water but focused on pKa calculations rather than the properties of the coiled coils themselves.…”