Dataset Information

PH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation.

ABSTRACT: Microsecond-long all-atom molecular dynamics (MD) simulations, circular dichroism, laser Doppler velocimetry, and dynamic light-scattering techniques have been used to investigate pH-induced changes in the secondary structure, charge, and conformation of poly l-lysine (PLL) and poly l-glutamic acid (PGA). The employed combination of the experimental methods reveals for both PLL and PGA a narrow pH range at which they are charged enough to form stable colloidal suspensions, maintaining their ?-helix content above 60%; an elevated charge state of the peptides required for colloidal stability promotes the peptide solvation as a random coil. To obtain a more microscopic view on the conformations and to verify the modeling performance, peptide secondary structure and conformations rising in MD simulations are also examined using three different force fields, i.e., OPLS-AA, CHARMM27, and AMBER99SB*-ILDNP. Ramachandran plots reveal that in the examined setup the ?-helix content is systematically overestimated in CHARMM27, while OPLS-AA overestimates the ?-sheet fraction at lower ionization degrees. At high ionization degrees, the OPLS-AA force-field-predicted secondary structure fractions match the experimentally measured distribution most closely. However, the pH-induced changes in PLL and PGA secondary structure are reasonably captured only by the AMBER99SB*-ILDNP force field, with the exception of the fully charged PGA in which the ?-helix content is overestimated. The comparison to simulations results shows that the examined force fields involve significant deviations in their predictions for charged homopolypeptides. The detailed mapping of secondary structure dependency on pH for the polypeptides, especially finding the stable colloidal ?-helical regime for both examined peptides, has significant potential for practical applications of the charged homopolypeptides. The findings raise attention especially to the pH fine tuning as an underappreciated control factor in surface modification and self-assembly.

SUBMITTER: Batys P

PROVIDER: S-EPMC7590956 | biostudies-literature | 2020 Apr

REPOSITORIES: biostudies-literature

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pH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation.

Batys Piotr P Morga Maria M Bonarek Piotr P Sammalkorpi Maria M

The journal of physical chemistry. B 20200326 14

Microsecond-long all-atom molecular dynamics (MD) simulations, circular dichroism, laser Doppler velocimetry, and dynamic light-scattering techniques have been used to investigate pH-induced changes in the secondary structure, charge, and conformation of poly l-lysine (PLL) and poly l-glutamic acid (PGA). The employed combination of the experimental methods reveals for both PLL and PGA a narrow pH range at which they are charged enough to form stable colloidal suspensions, maintaining their α-he ...[more]

PMID: 32182068

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Project description:Coarse-grained force fields for protein simulations are usually designed and parameterized to treat proteins composed of natural L-amino-acid residues. However, D-amino-acid residues occur in bacterial, fungal (e.g., gramicidins), as well as human-designed proteins. For this reason, we have extended the UNRES coarse-grained force field developed in our laboratory to treat systems with D-amino-acid residues. We developed the respective virtual-bond-torsional and double-torsional potentials for rotation about the C (?) · · · C (?) virtual-bond axis and two consecutive C (?) · · · C (?) virtual-bond axes, respectively, as functions of virtual-bond-dihedral angles ?. In turn, these were calculated as potentials of mean force (PMFs) from the diabatic energy surfaces of terminally-blocked model compounds for glycine, alanine, and proline. The potential-energy surfaces were calculated by using the ab initio method of molecular quantum mechanics at the Møller-Plesset (MP2) level of theory and the 6-31G(d,p) basis set, with the rotation angles of the peptide groups about [Formula: see text] and [Formula: see text] used as variables, and the energy was minimized with respect to the remaining degrees of freedom. The PMFs were calculated by numerical integration for all pairs and triplets with all possible combinations of types (glycine, alanine, and proline) and chirality (D or L); however, symmetry relations reduce the number of non-equivalent torsional potentials to 13 and the number of double-torsional potentials to 63 for a given C-terminal blocking group. Subsequently, one- (for torsional) and two-dimensional (for double-torsional potentials) Fourier series were fitted to the PMFs to obtain analytical expressions. It was found that the torsional potentials of the x-Y and X-y types, where X and Y are Ala or Pro, respectively, and a lowercase letter denotes D-chirality, have global minima for small absolute values of ?, accounting for the double-helical structure of gramicidin A, which is a dimer of two chains, each possessing an alternating D-Tyr-L-Tyr sequence, and similar peptides. The side-chain and correlation potentials for D-amino-acid residues were obtained by applying the reflection about the [Formula: see text] plane to the respective potentials for the L-amino-acid residues.

Dataset Information

PH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation.

Publications

pH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation.

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