Michael A. McAllister

Peptide models XV. The effect of basis set size increase and electron correlation on selected minima of the ab initio 2D-Ramachandran map of For-Gly-NH2 and For-L-Ala-NH2

A total of eleven basis sets from 3-21G to 6-3111++G(d,p) have been used at the HF and MP2 levels of theory for geometry optimizations of the global, γl, (φ = −75 °, Ψ = +75 °) and the second lowest, βl, (φ = −150 °, Ψ = + 150 °) minimum energy conformations of the l enantiomer of HCOue5f8NHue5f8CH(CH3)ue5f8COue5f8NH2. The results showed that due to fortuitous cancellation of correlation and basis set effects, the HF/3-21G energy-difference of these conformers agrees well with the MP2/6-311++G(d,p) energy difference, while the HF/6-311++G(d,p) energy difference converges erroneously toward zero. n nThe other legitimate conformers were optimized at the HF/3-21G, HF/6311++G(d,p), and MP2/6-311++G(d,p) levels of theory. The results showed that one of the minima disappeared at HF/6-311++G(d,p) and one more of the minima did not occur at the MP2/6-311++G(d,p) level of theory. The correlation and basis set effects stabilized the higher energy conformers.

Peptide models XIX: Side-chain conformational energy surface E = ƒ(χ1,χ2) and amide I vibrational frequencies of N-formyl-l-phenylalaninamide (For-Phe-NH2) in its γL or γinv or C7eq backbone conformation

In a study of cross sections of the E = ƒ(χ1,χ2) side-chain conformational potential energy surface of the γL or c7eq backbone conformation of For-l-Phe-NH2, it was found that there are three conformations (g +, a and g −) due to rotation about the Cαχ1 Cβ bond. It should be emphasised that the γL backbone conformation is conserved during rotation about χ1. However, there is only one unique conformation along the rotation about the Cβχ2 Ph bond. The ue5f8CH2ue5f8Ph group showed greater stabilisation, with respect to hydrogen (Gly), than the ue5f8CH3 (Ala) or ue5f8CH2ue5f8OH (Ser) substituents. The hydrogen-bonded Cue5fbO (amide 1) vibrational frequency is split into two bands due to the coupling of the Cue5fbO stretching and ue5f8NH2 scissoring modes of motion. The other carbonyl, not involved in hydrogen bonding, has a characteristic single IR band with a relatively high frequency. The orientation of the ue5f8Ph group has no appreciable effect on these vibrational frequencies.

Characterization of low-barrier hydrogen bonds 2. HF2−: a density functional and ab initio study

Abstract Hartree-Fock, Moller-Plesset, QCISD, CCSD, and DFT calculations have been carried out using the 6–31+G(d,p), 6–31+G(2d,p), 6–31+G(3d,2p), and 6–31+G(3df,2p) basis sets to study the interaction of a fluoride ion with hydrogen fluoride. In each case the resulting hydrogen bond is extremely strong, resulting in a single well potential, with no barrier for proton transfer. Density functional methods employing non-local gradient-corrected exchange and correlation functionals were found to perform very similarly to other correlated methods, including calculations at the MP2, QCISD, and CCSD levels of theory. DFT calculations using the local functional SVWN gave results in very poor agreement with the other methods. SVWN gave interaction energies about 10 kcal mol −1 too high when compared to recent gas phase experiments.

Characteristics of Ramachandran maps of L-alanine diamides as computed by various molecular mechanics, semiempirical and ab initio MO methods. A search for primary standard of peptide conformational stability

Abstract The optimized geometries and relative energies obtained by four force field and two semi-empirical methods were compared with ab initio results computed for formyl- L -alaninamide. Not all methods yielded the same number of minimum energy conformers. Furthermore, while the optimized geometries of the conformers found were comparable, the computed relative energies varied substantially. Also, the force field calculations produced Ramachandran maps that did not even have the appearance of the ab initio Ramachandran map. Correlating the ab initio relative energies (Δ E ) or free energy (Δ G ) with the log of relative populations, ln( p x / p γ L ), led to linear relationships from which four conformers deviated; two of them (α L and e L ) were overly destabilized and two of them (γ L and γ D ) were over-stabilized. It is suggested that, after such deviations are corrected, a primary standard may be obtained that might be useful in further investigations related to force-field parametrization as well as protein folding.

Low-barrier hydrogen bonds: Abinitio and DFT investigation

High‐level ab initio and DFT molecular orbital calculations have been used to investigate the physical properties of a model low‐barrier hydrogen bond (LBHB) system: formic acid–formate anion. In the gas phase, it is found that the hydrogen bond formed is extraordinarily short and strong [ca. 27 kcal/mol at B3LYP/6‐31++G(d,u2009p)], with a calculated enthalpy of activation for proton transfer from donor to acceptor that is less than the zero‐point vibrational energy available to the system. Several perturbations to this system were studied. Forcing a mismatch of pKas between donor and acceptor, via the use of substituents, causes the strength of the hydrogen bond to decrease. Microsolvation of the hydrogen‐bonded complex does not affect the strength of the low‐barrier hydrogen bond very much. Small variations in the structure of the LBHB results in a decrease in hydrogen‐bond strength. Increasing the effective polarity of the cavity surrounding the LBHB was found to have a significant impact on the strength of the hydrogen bond. Implications for enzyme catalysis are discussed.u2003© 1998 John Wiley & Sons, Inc.u2003J Comput Chem 19: 1345–1352, 1998

Characterization of low-barrier hydrogen bonds 4. Basis set and correlation effects: an ab initio and DFT investigation

Abstract High-level ab initio and density functional calculations conclude that formic acid and formate anion form a very short, strong hydrogen bond in the gas phase. This system is proposed as a model for the interactions present during many enzyme-catalysed reactions. The results of an extensive basis set study suggests that 6–31+G(d,p) is an excellent and sufficient basis set for the further study of these types of system. Hartree-Fock calculations consistently underestimated the energy of interaction between a formic acid and a formate anion (22 kcal mol−1) while overestimating the potential energy barrier for transfer of a proton from formic acid to formate anion (2 kcal mol−1). Calculations at correlated levels of theory, including DFT, show a stronger energy of interaction (hydrogen bond energy) between formic acid and formate anion (27 kcal mol−1), and predict little or no barrier (0.3 kcal mol−1) for proton transfer. The density functional methods (BLYP and B3LYP) perform almost identically to other correlated ab initio methods such as MP2, MP3, and MP4.

CHARACTERIZATION OF INTERMEDIATES ON THE 1O2 +R2S POTENTIAL ENERGY SURFACE. A HIGH-LEVEL AB INITIO STUDY

Abstract High-level ab initio correlated methods, including calculations at various Moller-Plesset, QCISD, and CCSD levels of theory, have been used to study the potential energy surface for the reaction of organic sulfides with singlet oxygen. This has led to the identification and characterization of two discrete intermediates during the oxidation of sulfides to sulfoxides. One intermediate has a persulfoxide structure ( 1 ) while the other is a structure involving a thiadioxirane ring ( 2 ). These results are in excellent agreement with experimental results. The relative importance of improving correlation treatment and basis set completeness are assessed.

Theoretical investigation of the role of hydrogen bonding during ketosteroid isomerase catalysis

Abstract Hartree–Fock, Moller–Plesset, and density functional calculations have been carried out using the 6-31+G(d,p) basis set to study the role of strong hydrogen bonding during the reaction catalyzed by Δ 5 -3-ketosteroid isomerase. Both the ‘low-barrier hydrogen bond’ and ‘cooperative hydrogen bond’ mechanisms were investigated, and found to be equally stabilizing. These results are consistent with recent NMR and X-ray data, which showed that under some conditions the LBHB mechanism appears to be operative, but under other conditions the cooperative hydrogen bond mechanism dominates.

Steric versus electronic control during the carbonylation of substituted thexylboranes. A semi-empirical investigation

Abstract AM1 and PM3 calculations have been carried out to study the reaction of substituted thexylboranes with carbon monoxide. Exhaustive investigation of the complete potential energy surfaces of thexylborane and several substituted derivatives was carried out in order to determine the relative importance of steric and electronic factors in determining the ability of thexylboranes to form stable adducts with carbon monoxide. It is concluded that the primary reason that methyl-isopropy-thexylborane forms a less stable adduct with CO than does dimethyl-thexylborane is because of the increased steric demands around the boron atom when one of the alkyl substituents on the thexylborane is branched. These results help to explain recent experimental observations regarding the reactivity of branched versus straight chain thexylboranes.

Reaction of methoxide ion with the Z- and E-isomers of O-methylbenzohydroximoyl cyanide. Theoretical calculations on the conformations of the tetrahedral intermediate

Theoretical calculations (HF/6–31u2005+u2005G*, MP2/6–31u2005+u2005G*//HF/6–31u2005+u2005G*, B3LYP/6–31u2005+u2005G*//HF/6–31u2005+u2005G*, HF-SCIPCM/6–31u2005+u2005G*//HF/6–31u2005+u2005G*, and B3LYP-SCIPCM/6–31u2005+u2005G*//HF/6–31u2005+u2005G*) were carried out on the tetrahedral intermediate RC(CN)(OCH3)—NOCH3−, where Ru2005=u2005C6H5, CH2CH or H, generated by nucleophilic attack of methoxide ion on (Z)- or (E)-O-methylhydroximoyl cyanide [RC(CN)NOCH3]. These calculations indicate that the staggered conformation 4C, which would lead to an E-substitution product, is approximately 7 (Ru2005=u2005H) or 8u2005kcalu2005mol−1 (Ru2005=u2005CH2CH) less stable than conformation 4A, which leads to a Z-substitution product. Furthermore, the lowest energy transition state leading to a Z-substitution product is approximately 5u2005kcalu2005mol−1 lower in energy than the lowest energy transition state leading to an E-substitution product. These results provide an explanation for the experimental results reported recently that (Z)-O-methylbenzohydroximoyl cyanide gives only the less thermodynamically stable Z-substitution product under conditions where the purported tetrahedral intermediate should have a long enough lifetime to establish an equilibrium between all the staggered conformations. Copyright