Dataset Information

Effects of temperature and salt concentration on the structural stability of human lymphotactin: insights from molecular simulations.

ABSTRACT: Extensive molecular dynamics (MD) simulations ( approximately 70 ns total) with explicit solvent molecules and salt ions are carried out to probe the effects of temperature and salt concentration on the structural stability of the human Lymphotactin (hLtn). The distribution of ions near the protein surface and the stability of various structural motifs are observed to exhibit interesting dependence on the local sequence and structure. Whereas chloride association to the protein is overall enhanced as the temperature increases, the sodium distribution in the C-terminal helical region and, to a smaller degree, the chloride distribution in the same region are found higher at the lower temperature. The similar trend is also observed in nonlinear Poisson-Boltzmann calculations with a temperature-dependent water dielectric constant, once conformational averaging over a series of MD snapshots is done. The unexpected temperature dependence in the ion distribution is explained on the basis of the cancellation of association entropy for ion-side chain pairs of opposite-charge and like-charge characters, which have positive and negative contributions, respectively. The C-terminal helix is observed to partially melt whereas a short beta strand forms at the higher temperature with little salt dependence. The N-terminal region, by contrast, develops partial helical structure at a higher salt concentration. These observed behaviors are consistent with solvent and salt screening playing an important role in stabilizing the canonical chemokine fold of hLtn.

SUBMITTER: Formaneck MS

PROVIDER: S-EPMC2600855 | biostudies-literature | 2006 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Effects of temperature and salt concentration on the structural stability of human lymphotactin: insights from molecular simulations.

Formaneck Mark S MS Ma Liang L Cui Qiang Q

Journal of the American Chemical Society 20060701 29

Extensive molecular dynamics (MD) simulations ( approximately 70 ns total) with explicit solvent molecules and salt ions are carried out to probe the effects of temperature and salt concentration on the structural stability of the human Lymphotactin (hLtn). The distribution of ions near the protein surface and the stability of various structural motifs are observed to exhibit interesting dependence on the local sequence and structure. Whereas chloride association to the protein is overall enhanc ...[more]

PMID: 16848488

Similar Datasets

Project description:We have modeled the structure of human lymphotactin (hLpnt), by homology modeling and molecular dynamics simulations. This chemokine is unique in having a single disulfide bond and a long C-terminal tail. Because other structural classes of chemokines have two pairs of Cys residues, compared to one in Lpnt, and because it has been shown that both disulfide bonds are required for stability and function, the question arises how the Lpnt maintains its structural integrity. The initial structure of hLpnt was constructed by homology modeling. The first 63 residues in the monomer of hLpnt were modeled using the structure of the human CC chemokine, RANTES, whose sequence appeared most similar. The structure of the long C-terminal tail, missing in RANTES, was taken from the human muscle fatty-acid binding protein. In a Protein Data Bank search, this protein was found to contain a sequence that was most homologous to the long tail. Consequently, the modeled hLpnt C-terminal tail consisted of both alpha-helical and beta-motifs. The complete model of the hLpnt monomer consisted of two alpha-helices located above the five-stranded beta-sheet. Molecular dynamics simulations of the solvated initial model have indicated that the stability of the predicted fold is related to the geometry of Pro78. The five-stranded beta-sheet appeared to be preserved only when Pro78 was modeled in the cis conformation. Simulations were also performed both for the C-terminal truncated forms of the hLpnt that contained one or two (CC chemokine-like) disulfide bonds, and for the chicken Lpnt (cLpnt). Our MD simulations indicated that the turn region (T30-G34) in hLpnt is important for the interactions with the receptor, and that the long C-terminal region stabilizes both the turn (T30-G34) and the five-stranded beta-sheet. The major conclusion from our theoretical studies is that the lack of one disulfide bond and the extension of the C-terminus in hLptn are mutually complementary. It is very likely that removal of two Cys residues sufficiently destabilizes the structure of a chemokine molecule, particularly the core beta-sheet, to abolish its biological function. However, this situation is rectified by the long C-terminal segment. The role of this long region is most likely to stabilize the first beta-turn region and alpha-helix H1, explaining how this chemokine can function with a single disulfide bond.

Project description:In this study, we examine the temperature dependence of free energetics of nanotube association using graphical processing unit-enabled all-atom molecular dynamics simulations (FEN ZI) with two (10,10) single-walled carbon nanotubes in 3 m NaI aqueous salt solution. Results suggest that the free energy, enthalpy and entropy changes for the association process are all reduced at the high temperature, in agreement with previous investigations using other hydrophobes. Via the decomposition of free energy into individual components, we found that solvent contribution (including water, anion, and cation contributions) is correlated with the spatial distribution of the corresponding species and is influenced distinctly by the temperature. We studied the spatial distribution and the structure of the solvent in different regions: intertube, intratube and the bulk solvent. By calculating the fluctuation of coarse-grained tube-solvent surfaces, we found that tube-water interfacial fluctuation exhibits the strongest temperature dependence. By taking ions to be a solvent-like medium in the absence of water, tube-anion interfacial fluctuation shows similar but weaker dependence on temperature, while tube-cation interfacial fluctuation shows no dependence in general. These characteristics are discussed via the malleability of their corresponding solvation shells relative to the nanotube surface. Hydrogen bonding profiles and tetrahedrality of water arrangement are also computed to compare the structure of solvent in the solvent bulk and intertube region. The hydrophobic confinement induces a relatively lower concentration environment in the intertube region, therefore causing different intertube solvent structures which depend on the tube separation. This study is relevant in the continuing discourse on hydrophobic interactions (as they impact generally a broad class of phenomena in biology, biochemistry, and materials science and soft condensed matter research), and interpretations of hydrophobicity in terms of alternative but parallel signatures such as interfacial fluctuations, dewetting transitions, and enhanced fluctuation probabilities at interfaces.

Dataset Information

Effects of temperature and salt concentration on the structural stability of human lymphotactin: insights from molecular simulations.

Publications

Effects of temperature and salt concentration on the structural stability of human lymphotactin: insights from molecular simulations.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets