Vibrational spectroscopic characteristics of secondary structure polypeptides in liquid water: Constrained MD simulation studies (original) (raw)
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Nonadiabatic vibrational dynamics and spectroscopy of peptides: A quantum-classical description
Chemical Physics, 2008
A quantum-classical description of the amide I vibrational spectrum of peptides in aqueous solution is given, which is concerned with the effects of nonadiabatic couplings between vibrational eigenstates. It consists of a classical molecular dynamics simulation of the conformational distribution of the system, density functional theory calculations of the conformation-dependent and solvent-induced frequency fluctuations, and a semiclassical description of the vibrational line shapes. The study shows that the adiabatic approximation usually employed in semiclassical line shape theory is generally not valid, because it assumes a time scale separation between the dynamics of the amide I mode (with a period of ≈20 fs) and the motion of the solvent and the peptide (which also exhibits sub-100 fs dynamics). A practical and general computational scheme is presented, which allows for the calculation of spectroscopic response functions by directly solving the nonadiabatically coupled time-dependent Schrödinger equation. Adopting trialanine and heptaalanine as representative examples, it is shown that nonadiabatic interactions may considerably change the overall shape as well as local details of the amide I spectrum.
Vibrational spectroscopy, 2006
Over the last 40 years the theoretical basis has been developed for using vibrational spectroscopy as a tool for peptide and protein structure analysis. In spite of these efforts it is still considered to be a low resolution technique, which cannot compete with NMR and X-ray crystallography. However, experimental and computational developments over the last 10 years have provided tools which make vibrational spectroscopy a much more powerful technique. This review focuses mostly, though not exclusively, on the use of the amide I mode for the structure analysis of polypeptides. It evaluates the physical basis of a variety of theoretical and experimental concepts and argues that only a combination of different techniques and spectroscopies can advance the field towards a more precise determination of dihedral angles in even highly heterogeneous polypeptides.
Chemical Physics Letters, 2018
We have combined infrared (IR) experiments with molecular dynamics (MD) simulations in solution at nite temperature to analyse the vibrational signature of the small oppy peptide Alanine-Leucine. IR spectra computed from rstprinciples MD simulations exhibit no distinct dierences between conformational clusters of α-helix or β-sheet-like folds with dierent orientations of the bulky leucine side chain. All computed spectra show two prominent bands, in good agreement with the experiment, that are assigned to the stretch vibrations of the carbonyl and carboxyl group, respectively. Variations in band widths and exact maxima are likely due to small uctuations in the backbone torsion angles.
2002
Nonlinear time-resolved vibrational spectroscopy is used to compare spectral broadening of the amide I band of the small peptide trialanine with that of N-methylacetamide, a commonly used model system for the peptide bond. In contrast to N-methylacetamide, the amide I band of trialanine is significantly inhomogeneously broadened. Employing classical molecular-dynamics simulations combined with density-functional-theory calculations, the origin of the spectral inhomogeneity is investigated.
Vibrational Analysis of Peptides, Polypeptides
2016
The Raman and ir spectra of a-helical polybglutarnic acid) have been assigned on the basis of a normal mode calculation for this structure. The force field was based on our previously refined mainchain force constants for a-polyb-alanine) and side-chain force constants for /3calcium-poly(L-glutamate). Despite the identical backbone a-hel-ical structures, significantly different frequencies are calculated, and observed, in the amide I11 and backbone stretch regions of a-poly(L-glutamic acid), as compared with a-poly(L-alanine). This clearly demonstrates the influence of side-chain structure on main-chain vibrational modes.
Journal of Physical Chemistry B, 2020
Vibrational circular dichroism (VCD) is one of the major spectroscopic tools to study peptides. Nevertheless, a full understanding of what determines the signs and intensities of VCD bands of these compounds in the amide I and amide II spectral regions is still far from complete. In the present work, we study the origin of these VCD signals using the general coupled oscillator (GCO) analysis, a novel approach that has recently been developed. We apply this approach to the ForValNHMe model peptide in both α-helix and β-sheet configurations. We show that the intense VCD signals observed in the amide I and amide II spectral regions essentially have the same underlying mechanism, namely, the through-space coupling of electric dipoles. The crucial role played by intramolecular hydrogen bonds in determining VCD intensities is also illustrated. Moreover, we find that the contributions to the rotational strengths, considered to be insignificant in standard VCD models, may have sizable magnitudes and can thus not always be neglected. In addition, the VCD robustness of the amide I and II modes has been investigated by monitoring the variation of the rotational strength and its contributing terms during linear transit scans and by performing calculations with different computational parameters. From these studiesand in particular, the decomposition of the rotational strength made possible by the GCO analysisit becomes clear that one should be cautious when employing measures of robustness as proposed previously.
Many classical antimicrobial peptides adopt an amphipathic helical structure at a water-membrane interface. Prior studies led to the hypothesis that a hinge near the middle of a helical peptide plays an important role in facilitating peptide-membrane interactions. Here, dynamics and vibrations of a designed hybrid antimicrobial peptide LM7-2 in solution were simulated to investigate its hinge formation. Molecular dynamics simulation results on the basis of the CHARMM36 force field showed that the α-helix LM7-2 bent around two or three residues near the middle of the peptide, stayed in a helix-hinge-helix conformation for a short period of time, and then returned to a helical conformation. High resolution computational vibrational techniques were applied on the LM7-2 system when it has α-helical and helix-hinge-helix conformations to understand how this structural change affects its inherent vibrations. These studies concentrated on the calculation of frequencies that correspond to backbone amide bands I, II, and III: vibrational modes that are sensitive to changes in the secondary structure of peptides and proteins. To that end, Fourier transforms were applied to thermal fluctuations in C-N-H angles, C-N bond lengths, and C=O bond lengths of each amide group. In addition, instantaneous all-atom normal mode analysis was applied to monitor and detect the characteristic amide bands of each amide group within LM7-2 during the MD simulation. Computational vibrational results indicate that shapes and frequencies of amide bands II and especially III were altered only for amide groups near the hinge. These methods provide high resolution vibrational information that can complement spectroscopic vibrational studies. They assist in interpreting spectra of similar systems and suggest a marker for the presence of the helix-hinge-helix motif. Moreover, radial distribution functions indicated an increase in the probability of hydrogen bonding between water and a hydrogen atom connected to nitrogen (HN) in such a hinge. The probability of intramolecular hydrogen bond formation between HN and an amide group oxygen atom within LM7-2 was lower around the hinge. No correlation has been found between the presence of a hinge and hydrogen bonds between amide group oxygen atoms and the hydrogen atoms of water molecules. This result 2 suggests a mechanism for hinge formation wherein hydrogen bonds to oxygen atoms of water replace intramolecular hydrogen bonds as the peptide backbone folds.
The Journal of Physical Chemistry B, 2004
Chain length and site dependencies of amide I local mode frequencies of R-helical polyalanines are theoretically studied by carrying out semiempirical quantum chemistry calculations. A theoretical model that can be used to quantitatively predict both the local amide I mode frequencies and coupling constants between two different local amide I modes is developed. Using this theoretical model and performing molecular dynamics simulation of an R-helical polyalanine in liquid water, we investigate conformational fluctuation and hydrogen-bonding dynamics by monitoring amide I frequency fluctuations. The instantaneous normal-mode analysis method is used to obtain densities of states of the one-and two-exciton bands and to quantitatively investigate the extent of delocalization of the instantaneous amide I normal modes. Also, by introducing a novel concept of the so-called weighted phase-correlation factor, the symmetric natures of the delocalized amide I normal modes are elucidated, and it is also shown that there is no unique way to classify any given amide I normal mode of the R-helical polyalanine in liquid water to be either A-mode-like or E 1 -mode-like. From the ensembleaveraged dipole strength spectrum and density of one-exciton states, the amide I infrared absorption spectrum is numerically calculated and its asymmetric line shape is theoretically described. Considering both transitions from the ground state to one-exciton states and those from one-exciton states to two-exciton states, we calculate the two-dimensional IR pump-probe spectra and directly compare them with recent experimental results. A brief discussion on the cross-peaks previously observed in the two-dimensional difference spectrum is presented.
Vibrational analysis of peptides, polypeptides, and proteins
International Journal of Peptide and …, 1985
The normal modes have been calculated for three kinds of low energy y-turn structures resulting from recent conformational energy calculations by Nkmethy. Frequencies have been computed for a y-turn, a mirror-related 7-turn, and an inverse y-turn of CH3-CO-(L-Ala),-NH-CH3, with n = 3 and n = 5 , and for certain l4 C and l5 N derivatives of the n = 3 molecule. Correlations are evident between amide frequencies and y-turn structures, and it is found that only amide I modes of peptide groups in the turn are relatively insensitive to the lengths of attached chains.
Ab initio based building block model of amide I vibrations in peptides
Chemical Physics Letters, 2007
Various methods to parameterize an exciton model of amide I vibrations are suggested and analyzed. In the spirit of a systematic fragmentation scheme, small model peptides are employed as building-blocks to construct the vibrations of a polypeptide. As an example, extensive density functional theory (DFT) calculations at the B3LYP/6-31+G(d) theoretical level of glycine tripeptide are presented, which serve as reference data for testing various approximate schemes. The combination of a DFT description of next-neighbor interactions via dipeptide building blocks combined with an electrostatic model to account for the long-range interactions appears as a promising approach to achieve spectroscopic accuracy at low computational cost.