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We propose a new approach for force field optimizations which aims at reproducing dynamics characteristics using biomolecular MD simulations, in addition to improved prediction of motionally averaged structural properties available from experiment. As the source of experimental data for dynamics fittings, we use 13C NMR spin-lattice relaxation times T1 of backbone and sidechain carbons, which allow to determine correlation times of both overall molecular and intramolecular motions. For structural fittings, we use motionally averaged experimental values of NMR J couplings. The proline residue and its derivative 4-hydroxyproline with relatively simple cyclic structure and sidechain dynamics were chosen for the assessment of the new approach in this work. Initially, grid search and simplexed MD simulations identified large number of parameter sets which fit equally well experimental J couplings. Using the Arrhenius-type relationship between the force constant and the correlation time, the available MD data for a series of parameter sets were analyzed to predict the value of the force constant that best reproduces experimental timescale of the sidechain dynamics. Verification of the new force-field (termed as AMBER99SB-ILDNP) against NMR J couplings and correlation times showed consistent and significant improvements compared to the original force field in reproducing both structural and dynamics properties. The results suggest that matching experimental timescales of motions together with motionally averaged characteristics is the valid approach for force field parameter optimization. Such a comprehensive approach is not restricted to cyclic residues and can be extended to other amino acid residues, as well as to the backbone. Proteins 2014; 82:195–215. © 2013 Wiley Periodicals, Inc.

Historical collagen-based parchments have been studied by solid-state NMR. In addition, new parchment (produced according to traditional methods) and gelatin from bovine skin were also studied. Wideline 1H and MAS 13C measurements were carried out directly on intact parchments. A simple approach is proposed for evaluation of the extent of parchment degradation based on the linewidth changes in the 13C CPMAS spectra relative to new parchment and gelatin. Structural (bound) water content was estimated from wideline 1H NMR lineshape and relaxation time measurements. It was found that the relative water content in parchments correlates linearly with 13C MAS linewidths. Its decrease on parchment degradation indicates that structural water molecules are of primary importance in stabilizing higher order collagen structures. Backbone and side chain dynamics of collagen in parchments were compared to those of gelatin based on the 13C dipolar-dephased experiments. Carbonyl 13C chemical shift anisotropies were measured to deduce the geometry of the collagen backbone motion. Unlike previous studies, we found that the collagen backbone motion is similar to that found in other proteins and occurs primarily via small-angle librations about internal bond directions.

In view of the range of properties required from supramolecular materials, there is clearly a need for new strong quadruple hydrogen bonded modules, which can be used in polymer or copolymer synthesis via the self- or hetero-association of complimentary units. A cytosine-based module has been prepared for supramolecular applications using a straightforward synthetic approach. The cytosine module was designed such that it does not undergo tautomeric changes observed with ureidopyrimidinones. The cytosine module was capable of forming quadruple hydrogen bonded assemblies both in solution and in the solid state, and the structure of the dimeric self-assembled unit was confirmed by single-crystal X-ray and solution NMR techniques. The dimerization constant was estimated to be greater than 9 × 106 M-1 in deuterated benzene. The capacity of the cytosine-based module to strongly hetero-associate with the ureidopyrimidinone module was demonstrated, and a supramolecular polymer of a bifunctional unit incorporating the cytosine module and PEG-based linker was described.

ABSTRACT:1 H NMR chemical shifts have been obtained in the solvents deuterochloroform and dimethyl sulfoxide. The difference in the chemical shifts of an OH or NH group in these two solvents, Δδ = δ(DMSO) − δ(CDCl 3 ), can be converted into the hydrogen bond acidity, A, of the group using the equation A = 0.0065 + 0.133Δδ. The NMR A value, A NMR , can be used as a quantitative assessment of intramolecular hydrogen bonding. We list values of Δδ and A NMR for 55 compounds containing an OH group and 60 compounds with an NH group. For the hydroxy compounds, if A > 0.5 then the OH group is not part of an intramolecular hydrogen bond, but if A < 0.1 then the OH group forms part of an intramolecular hydrogen bond. For NH compounds, if A > 0.16 the NH group is not part of an intramolecular hydrogen bond, and if A < 0.05 the NH group is part of an intramolecular hydrogen bond. No comparison compounds are needed, and the method is extremely simple. We further show how it is possible to relate intramolecular hydrogen bonding to the actual effect on values of a number of physicochemical, environmental, and biochemical properties. ■ INTRODUCTION Shalaeva et al.1 have recently shown that the presence of an intramolecular hydrogen bond (intraHB) in a molecule can considerably alter the properties of a molecule. These include properties relevant to drug design such as solubility, permeability, and partition. It is therefore important to be able to identify molecules that possess intraHBs and, if possible, to assess the effect of an intraHB on the molecular properties. Testa and co-workers 2−5 were the first to show that the effect of intraHBs could be observed in water−solvent partition coefficients (as log P) and particularly in differences between partition coefficients in water−octanol and water−aprotic solvent systems. They set out differences in log P for water− octanol and water−heptane partitions (eq 1) and showed that intraHBs greatly reduce the value of Δ(log P) oct−hept . They also observed similar effects due to intraHBs in other water−octanol and water−solvent systems.4,5 Leo 6 used octanol and chloroform as the two solvent systems in order to calculate the hydrogen bond acidity of a solute, and Feng et al. 7 used dibutyl ether and cyclohexane as the solvent systems to calculate solute hydrogen bond acidity.

Crystalline layered carbon nitrides can be inter-converted by simple ion exchange process allowing their properties to be tuned.

Isolated model anion chromophores of the green and cyan fluorescent proteins were generated in an electrospray ion source, and their photodetachment spectra were recorded using photoelectron imaging. Vertical photodetachment energies of 2.85(10) and 4.08(10) eV have been measured for the model green fluorescent protein chromophore anion, corresponding to photodetachment from the ground electronic state of the anion to the ground and first excited electronic states of the radical, respectively. For the model cyan fluorescent protein chromophore anion, vertical photodetachment energies of 2.88(10) and 3.96(10) eV have been measured, corresponding to detachment from the ground electronic state of the anion to the ground and first excited electronic states of the neutral radical, respectively. We also find evidence suggesting that autoionization of electronically excited states of the chromophore anions competes with direct photodetachment. For comparison and to benchmark our measurements, the vertical photodetachment energies of deprotonated phenol and indole anions have also been recorded and presented. Quantum chemistry calculations support our assignments. We discuss our results in the context of the isolated protein chromophore anions acting as electron donors, one of their potential biological functions.

The results of the ring conformational analysis of L-proline, N-acetyl-L-proline, and trans-4-hydroxy-L-proline by NMR combined with calculations using density functional theory (DFT) and molecular dynamics (MD) are reported. Accurate values of 1H-1H J-couplings in water and other solvents have been determined. Using a two-site equilibrium model, the Cgamma-endo conformer of L-proline in water has been identified as intermediate between gammaTdelta [twist(Cgamma-endo, Cdelta-exo)] and gammaE [envelope(Cgamma-endo)] and the Cgamma-exo conformer as betaTgamma. Both conformers were equally populated at room temperature. The N-acetyl [cis-rotamer gammaTbeta(80%)/gammaE(20%) and trans-rotamer gammaTbeta(61%)/gammaE(39%)] and 4-hydroxy (gammaEpsilon) derivatives showed significant changes in both the population and the geometries of the preferred ring conformers. The combination of NMR predicted populations with the DFT B3LYP/6-311+G(2d,p)/IEFPCM calculations proved successful, resulting in fairly accurate predictions of J-couplings. Simulations using MD were mostly in favor of the two-site equilibrium model between Cgamma-endo and Cgamma-exo conformers, similar to that used for the analysis of NMR J-couplings. Various force fields examined for MD simulations failed to reproduce the ring conformational geometries and populations of L-proline in water accurately, while significantly better agreement with NMR was found for trans-N-acetyl-L-proline using GROMOS and AMBER force fields.