Exploring the Conserved Water Site and Hydration of a Coiled‐Coil Trimerisation Motif: A MD Simulation Study

Abstract

The solvent structure and dynamics around ccbeta-p, a 17-residue peptide that forms a parallel three-stranded alpha-helical coiled coil in solution, was analysed through 10 ns explicit solvent molecular dynamics (MD) simulations at 278 and 330 K. Comparison with two corresponding simulations of the monomeric form of ccbeta-p was used to investigate the changes of hydration upon coiled-coil formation. Pronounced peaks in the solvent density distribution between residues Arg8 and Glu13 of neighbouring helices show the presence of water bridges between the helices of the ccbeta-p trimer; this is in agreement with the water sites observed in X-ray crystallography experiments. Interestingly, this water site is structurally conserved in many three-stranded coiled coils and, together with the Arg and Glu residues, forms part of a motif that determines three-stranded coiled-coil formation. Our findings show that little direct correlation exists between the solvent density distribution and the temporal ordering of water around the trimeric coiled coil. The MD-calculated effective residence times of up to 40 ps show rapid exchange of surface water molecules with the bulk phase, and indicate that the solvent distribution around biomolecules requires interpretation in terms of continuous density distributions rather than in terms of discrete molecules of water. Together, our study contributes to understanding the principles of three-stranded coiled-coil formation.

Adsorption of Insulin Peptide on Charged Single‐Walled Carbon Nanotubes: Significant Role of Ordered Water Molecules

“…This inconsistency is similar to the weak correlation between the solvent number density distribution and the distribution of the residence times of the water molecules in the hydration shell of the de novo designed 17-residue ccb-p peptide in a recent study. [46] The trends of the numbers of hydrogen bonds between ICB and the two hydration shells (d) are similar to that between ICB and the first hydration shell (c) as we discussed, which also confirms the important role of water in the peptide adsorption onto the CNT surfaces. Figure 10b shows the numbers of water-water hydrogen bonds in these hydration shells.…”

Crystal structure of a trimeric form of the KV7.1 (KCNQ1) A‐domain tail coiled‐coil reveals structural plasticity and context dependent changes in a putative coiled‐coil trimerization motif

“…4(C)] that is thought to play a key role in stabilization of this architecture. 49 Kammerer et al proposed that the sequence motif R-h-x-x-h-E is a universal determinant for trimeric coiled-coils and that interactions made by this motif could dominate the effects of the hydrophobic core regions of short coiled-coils. 16 Consistent with this observation, we find that the R-h-x-x-h-E motif is crucial for the trimeric assembly of Q1-short [ Fig.…”

The clear and dark sides of water: influence on the coiled coil folding domain

“…The residue based coiled coil stability of about -1.2 kcal/mol, ΔG residue , is a good indicator of the sum of electrostatic and dispersive interactions operative between residues, with an entropy term of about -0.3 kcal/ mol per residue. The coiled coil stability is inversely proportional to the polypeptide chain length and directly to the side chain salt-bridges of residues at positioning e and g (electrostatic interaction between e of one 'heptad' and g' of the following 'heptad' on the other helix are operative) (11,19). For the electrostatic interaction part of the above shown -1.2 kcal/mol sum, the following values are given in the literature: ~ -0.37 kcal/mol (9,19).…”

“…Although the residues mutated, these key waters are structurally conserved and together with Arg-Glu residues they determine the three-stranded coiled coil structure. This 'water-bridge-concept' is enforced by most X-ray crystallographic data, too (11).…”