The nonplanarity of the peptide group: Molecular dynamics simulations with a polarizable two-state model for the peptide bond

Rick, Steven W.; Cachau, Raúl E.

doi:10.1063/1.481078

Cited by 35 publications

(36 citation statements)

References 78 publications

(104 reference statements)

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“…The large number of investigations reflects the subtlety of the issues related to planarity. Although the most recent computational 3,5 and experimental (empirical) 6 studies proved beyond reasonable doubt the C s point-group symmetry of the Born-Oppenheimer equilibrium structure, r e BO , of formamide, an r e BO consistent with all available experimental and quantum chemical information has not been derived. An aim of the present study thus has been to derive a representation of the equilibrium structure of formamide.…”

Section: Introductionmentioning

confidence: 99%

“…Whatever is the most pedagogical interpretation of the assumed planarity of the XC(dO)NHY linkage, contributions of resonance structures can be changed by interactions with the environment of the linkage represented by the substituents X and Y, which may result in deviations from planarity. [2][3][4][5] Furthermore, it is shown in this study that many of the molecules containing the XC(dO)NHY linkage are not planar at equilibrium. Therefore, explaining their planar ground-state structure by arguments based on equilibrium properties is somewhat controversial.…”

Section: Introductionmentioning

confidence: 99%

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Equilibrium vs Ground-State Planarity of the CONH Linkage

et al. 2007

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Planarity of the XC(d)NHY linkage has been investigated in unprecedented detail in a number of relatively simple compounds, including formamide (, and methyl carbamate (X ) OCH 3 , Y ) H). Reliable estimates of the equilibrium structures of formamide, cyanamide, acetamide, urea, carbamic acid, methylamine, dimethyl ether, and methyl carbamate are derived, mostly for the first time. It is shown that formamide, considered prototypical for the amide linkage, is not typical as it has a planar equilibrium amide linkage corresponding to a single-minimum inversion potential around N. In contrast, several molecules containing the CONH linkage seem to have a pyramidalized nitrogen at equilibrium and a double-minimum inversion potential with a very small inversion barrier allowing for an effectively planar ground-state structure. Observables of rotational spectroscopy, including ground-state inertial defects, quadrupole coupling and centrifugal distortion constants, and dipole moment components, as well as equilibrium CdO and C-N bond lengths are reviewed in their ability to indicate the planarity of the effective and possibly the equilibrium structures.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Equilibrium vs Ground-State Planarity of the CONH Linkage

et al. 2007

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“…[20][21][22][23][24][25][26][27][28] Another model allows for charge to move from atom to atom as well from atom to bond. 29 Other models combine both inducible dipoles and fluctuating charges. 30,31 The fluctuating charge models have a polarization response only along the directions connecting charge sites, generally placed on or near atoms.…”

Section: Introductionmentioning

confidence: 99%

Simulations of ice and liquid water over a range of temperatures using the fluctuating charge model

Rick

2001

The Journal of Chemical Physics

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178

159

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Simulations of ice and liquid water over a range of temperatures using the fluctuating charge model The temperature dependence of the thermodynamic and dynamical properties of liquid water using the polarizable fluctuating charge ͑FQ͒ model is presented. The properties of ice Ih, both for a perfect lattice with no thermal disorder and at a temperature of 273 K, are also presented. In contrast to nonpolarizable models, the FQ model has a density maximum of water near 277 K. For ice, the model has a dipole moment of the perfect lattice of 3.05 Debye, in good agreement with a recent induction model calculation. The simulations at 273 K and the correct density find that thermal motion decreases the average dipole moment to 2.96 D. The liquid state dipole moment is less than the ice value and decreases with temperature.

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“…The accuracy of the experimental data allows observation of individual electron densities for each atom (seefig. 5), deviations from the spherical atom model in an electron difference map, correlations between C-O and C-N bond lengths and some deviations of the w angle in peptide bonds[20], unusually short distances CH-O, ordered solvent molecules and 54 % of all the possible atoms in the protein. This last fact permits the unequivocal assignement of the protonation states in the active site zone (a well-ordered region with B-factors between 3 and 5 Å 2 ).…”

mentioning

confidence: 98%

Subatomic and atomic crystallographic studies of aldose reductase: implications for inhibitor binding

Podjarny

Cachau

Schneider

et al. 2004

Cellular and Molecular Life Sciences (CMLS)

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The determination of several of aldose reductase-inhibitor complexes at subatomic resolution has revealed new structural details, including the specific interatomic contacts involved in inhibitor binding. In this article, we review the structures of the complexes of ALR2 with IDD 594 (resolution: 0.66 angstrom, IC50 (concentration of the inhibitor that produced half-maximal effect): 30 nM, space group: P2(1)), IDD 393 (resolution: 0.90 angstrom, IC50: 6 nM, space group: P1), fidarestat (resolution: 0.92 angstrom, IC50: 9 nM, space group: P2(1)) and minalrestat (resolution: 1.10 angstrom, IC50: 73 nM, space group: P1). The structures are compared and found to be highly reproductible within the same space group (root mean square (RMS) deviations: 0.15 approximately 0.3 angstrom). The mode of binding of the carboxylate inhibitors IDD 594 and IDD 393 is analysed. The binding of the carboxylate head can be accurately determined by the subatomic resolution structures, since both the protonation states and the positions of the atoms are very precisely known. The differences appear in the binding in the specificity pocket. The high-resolution structures explain the differences in IC50, which are confirmed both experimentally by mass spectrometry measures of VC50 and theoretically by free energy perturbation calculations. The binding of the cyclic imide inhibitors fidarestat and minalrestat is also described, focusing on the observation of a Cl(-) ion which binds simultaneously with fidarestat. The presence of this anion, binding also to the active site residue His110, leads to a mechanism in which the inhibitor can bind in a neutral state and then become charged inside the active site pocket. This mechanism can explain the excellent in vivo properties of cyclic imide inhibitors. In summary, the complete and detailed information supplied by the subatomic resolution structures can explain the differences in binding energy of the different inhibitors.

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The nonplanarity of the peptide group: Molecular dynamics simulations with a polarizable two-state model for the peptide bond

Cited by 35 publications

References 78 publications

Equilibrium vs Ground-State Planarity of the CONH Linkage

Equilibrium vs Ground-State Planarity of the CONH Linkage

Simulations of ice and liquid water over a range of temperatures using the fluctuating charge model

Subatomic and atomic crystallographic studies of aldose reductase: implications for inhibitor binding

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