Dataset Information

Peptide and Protein Structure Prediction with a Simplified Continuum Solvent Model.

ABSTRACT: A continuum solvent model based on screened Coulomb potentials has been simplified and parametrized to sample native-like structures in replica-exchange simulations of each of six different peptides and miniproteins. Low-energy, native, and non-native structures were used to iteratively refine 11 parameter values. The centroid of the largest cluster of structures sampled in simulations initiated from an extended conformation represents the predicted structure. The main-chain rms deviation of this prediction from the experimental structure was 0.47 Å for the 12-residue Trp-zip2, 0.86 Å for the 14-residue MBH12, 2.53 Å for the 17-residue U(1-17)T9D, 2.03 Å for the 20-residue BS1, 1.08 Å for the 20-residue Trp-cage, and 3.64 Å for the 35-residue villin headpiece subdomain HP35. The centroid of the sixth largest cluster sampled for HP35 deviated by 0.91 Å. The CHARMM22/CMAP force field was used, with an additional ? torsion term for residues other than glycine and proline. Six parameters govern the dielectric response of the continuum solvent, and four values of surface tension approximate nonpolar effects. An atom's self-energy and interaction energies are screened independently, each depending on whether the atom is part of a charged group, a neutral hydrogen-bonding main-chain group, or any other neutral group. The parameters inferred result in strong main-chain hydrogen bonds, consistent with the view that protein folding is dominated by the formation of these bonds. (1,2) Conformations of MBH12 and BS1 were excluded from the energy-function refinement, suggesting the parameters, referred to as SCP18, are transferable. An efficient estimate of solvent-accessible surface area is also described.

SUBMITTER: Steinbach PJ

PROVIDER: S-EPMC6741432 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Peptide and Protein Structure Prediction with a Simplified Continuum Solvent Model.

Steinbach Peter J PJ

The journal of physical chemistry. B 20181005 49

A continuum solvent model based on screened Coulomb potentials has been simplified and parametrized to sample native-like structures in replica-exchange simulations of each of six different peptides and miniproteins. Low-energy, native, and non-native structures were used to iteratively refine 11 parameter values. The centroid of the largest cluster of structures sampled in simulations initiated from an extended conformation represents the predicted structure. The main-chain rms deviation of thi ...[more]

PMID: 30230838

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Project description:Alamethicin is a 20-amino acid antibiotic peptide that forms voltage-gated ion channels in lipid bilayers. Here we report calculations of its association free energy with membranes. The calculations take into account the various free-energy terms that contribute to the transfer of the peptide from the aqueous phase into bilayers of different widths. The electrostatic and nonpolar contributions to the solvation free energy are calculated using continuum solvent models. The contributions from the lipid perturbation and membrane deformation effects and the entropy loss associated with peptide immobilization in the bilayer are estimated from a statistical thermodynamic model. The calculations were carried out using two classes of experimentally observed conformations, both of which are helical: the NMR and the x-ray crystal structures. Our calculations show that alamethicin is unlikely to partition into bilayers in any of the NMR conformations because they have uncompensated backbone hydrogen bonds and their association with the membrane involves a large electrostatic solvation free energy penalty. In contrast, the x-ray conformations provide enough backbone hydrogen bonds for the peptide to associate with bilayers. We tested numerous transmembrane and surface orientations of the peptide in bilayers, and our calculations indicate that the most favorable orientation is transmembrane, where the peptide protrudes approximately 4 A into the water-membrane interface, in very good agreement with electron paramagnetic resonance and oriented circular dichroism measurements. The calculations were carried out using two alamethicin isoforms: one with glutamine and the other with glutamate in the 18th position. The calculations indicate that the two isoforms have similar membrane orientations and that their insertion into the membrane is likely to involve a 2-A deformation of the bilayer, again, in good agreement with experimental data. The implications of the results for the biological function of alamethicin and its capacity to oligomerize and form ion channels are discussed.

Dataset Information

Peptide and Protein Structure Prediction with a Simplified Continuum Solvent Model.

Publications

Peptide and Protein Structure Prediction with a Simplified Continuum Solvent Model.

Similar Datasets

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