Noemi G. Mirkin

Potential energy functions: From consistent force fields to spectroscopically determined polarizable force fields

We review our methodology for producing physically accurate potential energy functions, particularly relevant in the context of Lifsons goal of including frequency agreement as one of the criteria of a self‐consistent force field. Our spectroscopically determined force field (SDFF) procedure guarantees such agreement by imposing it as an initial constraint on parameter optimization, and accomplishes this by an analytical transformation of ab initio “data” into the energy function format. After describing the elements of the SDFF protocol, we indicate its implementation to date and then discuss recent advances in our representation of the force field, in particular those required to produce an SDFF for the peptide group.

Conformers of trans-N-methylacetamide : Ab initio study of geometries and vibrational spectra

Energies and geometries have been obtained, at the 4-31G* level, for the four stable conformers of trans.N-methylacetamide that result from conformational isomerism of the CH, groups. Ab initio force fields were obtained for these four structures, and the force constants were scaled to experimental matrix-isolated frequencies. The results show that the conformers should be spectroscopically distinguishable, and in fact the observed bands can be satisfactorily assigned on this basis without invoking a non-planar amide group. Conformational isomerism may also be partly responsible for the unusual breadth of the amide V band.

A spectroscopically effective molecular mechanics model for the intermolecular interactions of the hydrogen-bonded N-methylacetamide dimer

Abstract An MP2/6-31+G ∗ calculation of the N -methylacetamide dimer shows that it has two minimum energy structures, both hydrogen bonded with peptide planes roughly perpendicular to each other. A complete molecular mechanics optimization of the dimer has been done, using a model for the intermolecular interactions consisting of charges, atomic dipoles, and van der Waals interactions and the methodology of our spectroscopically determined force field for the intramolecular interactions. The two structures are satisfactorily reproduced, as are their interaction energies, their dipole moments, and, from the point of view of our goal of a spectroscopically accurate force field, their six intermolecular normal mode frequencies.

AB INITIO VIBRATIONAL ANALYSIS OF ISOTOPIC DERIVATIVES OF AQUEOUS HYDROGEN-BONDED TRANS-N-METHYLACETAMIDE

Abstract Normal modes have been calculated for a CH 3 CONHCH 3 (H 2 O) 2 [NMA(H 2 O) 2 ] system and its CCD 3 , NCD 3 , 13 C 15 N, and ND derivatives. Fully optimized structures were obtained with the 6–31+ G ∗ basis set. The scale factors for the NMA force constants were obtained by optimizing the scale factors for the isolated molecule to experimental frequencies of aqueous NMA. HOH bend scale factors were found that are consistent with observed resonance Raman enhancements and infrared intensities of the components of the amide I doublet. Its frequency splitting can be reproduced quantitatively by a reaction field calculation. The calculated frequency difference between the two allowed NMA conformers confirms the assignment of the two observed amide II bands to the presence of these conformers in aqueous solution. An evaluation is made of the assignments of other bands.

A polarizable electrostatic model of the N-methylacetamide dimer

Our previously developed polarizable electrostatic model is applied to isolated N‐methylacetamide (NMA) and to three hydrogen‐bonded configurations of the NMA dimer. Two versions of the model are studied. In the first one (POL1), polarizability along the valence bonds is described by induced bond charge increments, and polarizability perpendicular to the bonds is described by cylindrically isotropic induced atomic dipoles. In the other version (POL2), the induced bond charge increments are replaced by induced atomic dipoles along the bonds. The parameterization is done by fitting to ab initio MP2/6‐31++G(d,p) electric potentials. The polarizability parameters are determined by subjecting the NMA molecule to various external electric fields. POL1 turns out to be easier to optimize than POL2. Both models reproduce well the ab initio electric potentials, molecular dipole moments, and molecular polarizability tensors of the monomer and the dimers. Nonpolarizable models are also investigated. The results show that polarization is very important for reproducing the electric potentials of the studied dimers, indicating that this is also the case in hydrogen bonding between peptide groups in proteins.

Structure of trans-N-methylacetamide: planar or non-planar symmetry?

Abstract The structure of trans-N-methylacetamide has been fully optimized, i.e., all frequencies real, at the Hartree-Fock (HF) level with twelve basis sets from 6G–31G∗ through 6–311 + + G∗∗ and with electron correlation at the second-order Moller-Plesset perturbation level (MP2) with the 6G–31G∗, 6G–311G∗∗, 6–31 + G∗, 6–311 + G∗, and 6–311 + + G∗∗ basis sets. Minimum energy structures are non-planar at HF and MP2 levels without diffuse functions. With diffuse functions included, the minimum energy structure is planar for all basis sets at the HF level and tends toward planarity at more complete levels of MP2 electron correlation. These results, as well as MP3, MP4 (SDQ), and CISD optimizations without frequency calculations, lead us to conclude that, within the expected torsion angle variations in such calculations, the equilibrium structure of the isolated molecule has planar symmetry.

A quantitative anharmonic analysis of the amide A band in α-helical poly( L -alanine)

Polarized ir spectra of oriented films ofa-helical poly(L-alanine) (a-PLA) have been obtained as a function of residual solvent dichloroacetic acid (DCA). The amide A, B, II, and V regions exhibit multiple bands whose structure depends on the residual DCA content, and those associated with the aI-PLA structure have been identified. A calculation of the relevant cubic anharmonic force constants indicates that, contrary to previous assignments, the overtone of amide II(A) is in Fermi resonance with the NH stretch fundamental, whose unperturbed frequency we now find to be at 3314 cm 21 , significantly higher than the previously suggested 3279 cm 21 . The presence of a structure in addition to the standardaI-PLA is indicated by our analysis.

Regular paperAb initio vibrational analysis of isotopic derivatives of aqueous hydrogen-bonded trans-N-methylacetamide

Normal modes have been calculated for a CH3CONHCH3(H2O)2[NMA(H2O)2] system and its CCD3, NCD3, 13C15N, and ND derivatives. Fully optimized structures were obtained with the 6–31+G∗ basis set. The scale factors for the NMA force constants were obtained by optimizing the scale factors for the isolated molecule to experimental frequencies of aqueous NMA. HOH bend scale factors were found that are consistent with observed resonance Raman enhancements and infrared intensities of the components of the amide I doublet. Its frequency splitting can be reproduced quantitatively by a reaction field calculation. The calculated frequency difference between the two allowed NMA conformers confirms the assignment of the two observed amide II bands to the presence of these conformers in aqueous solution. An evaluation is made of the assignments of other bands.

Peptide C(alpha)D(alpha) stretch frequencies in a hydrated conformation are perturbed mainly by C(alpha)-D(alpha)...O hydrogen bonding.

We have shown (J. Phys. Chem. A 2004, 108, 10923; 2007, 111, 5300) that the C(alpha)D(alpha) stretch frequency, nu(CD), can discriminate between uniform alpha(R), beta, and polyproline II conformations of isolated peptides. Similar results for such peptides to which explicit waters are hydrogen bonded exhibit shifts in nu(CD) from those of the isolated structures. We demonstrate that the main source of these frequency shifts is the formation of C(alpha)-D(alpha)...O hydrogen bonds to water. Taking into account C-H...O(water) hydrogen bonding, together with the traditional bonding of peptide groups to water, can be expected to increase our understanding of the interaction of proteins with their aqueous environment.

Conformation dependence of the CαDα stretch mode in peptides. II. Explicitly hydrated alanine peptide structures

Our previous studies of the potential utility of the CαDα stretch frequency, ν(CD), as a tool for determining conformation in peptide systems (Mirkin and Krimm, J Phys Chem A 2004, 108, 10923–10924; 2007, 111, 5300–5303) dealt with the spectroscopic characteristics of isolated alanine peptides with αR, β, and polyproline II structures. We have now extended these ab initio calculations to include various explicit‐water environments interacting with such conformers. We find that the structure‐discriminating feature of this technique is in fact enhanced as a result of the conformation‐specific interactions of the bonding waters, in part due to our finding (Mirkin and Krimm, J Phys Chem B 2008, 112, 15268) that CαDα…O(water) hydrogen bonds can be present in addition to those expected between water and the CO and NH of the peptide groups. In fact, ν(CD) is hardly affected by the latter bonding but can be shifted by up to 70 cm−1 by the former hydrogen bonds. We also discuss the factors that will have to be considered in developing the molecular dynamics (MD) treatment needed to satisfactorily take account of the influence of outer water layers on the structure of the first‐layer water molecules that hydrogen bond to the peptide backbone.