摘要:

AbstractThe stochastic search method was employed to find as many conformers on the MM2 and MM3 energy surfaces as possible for cyclic saturated hydrocarbons with ring sizes from 9 through 12. The number found was 8 MM2 (8 MM3) for 9 rings, 18 MM2 (16 MM3) for 10 rings, 40 MM2 (29 MM3) for 11 rings, and 111 MM2 (90 MM3) for 12 rings. A measure of similarity between pairs of conformers of a compound, called conformational distance, is described. It was used to correlate similar MM2 and MM3 conformers. It was discovered that some conformers on each energy surface are not close to minima on the other surface in rings larger than 9. On refinement with the other optimizer, they changed considerably—going downhill to other previously found minima on the other energy surface or (in a few cases) going to minima which had not been found by direct searches. Conformational distance was also employed as an indication of which pairs of MM2 (or MM3) conformers are likely to interconvert rapidly. A new stochastic procedure of using small kicks was used to search for the most likely interconversion processes among the conformers. There is fairly good agreement between the most facile pathways located by it and unusually short conformational distances. Several additional 12‐ring conformers (not found with previous methods) were located through application of this small kick proced

ISSN:0192-8651    

DOI:10.1002/jcc.540120602

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractA new strategy for the determination of force parameters is presented. The equilibrium values appearing in the force field equations representing the “stretching” and “bending” of bonds are directly determined from quantum mechanical calculations without geometrical restrictions. The determination of the force parameters is carried out by means of a rigorous fitting between the quantum mechanic and the molecular mechanical energy variations arising from the perturbation of the geometric variables. The strategy presented here has been incorporated into a computer program named PAPQMD, which was developed in order to provide nonquantum mechanical experts with a powerful tool for the determination of approximate force parameters. The program was developed upon the assumption that force parameters are not universal, but they strongly depend on the molecular environment. This implies that the parametrization procedure should be done in a molecular model close to the molecule or molecules to be studied by means of molecular mechanical or dynamic methods, and consequently, it is no longer supposed that the variation of one geometrical parameter does not affect the rest of the molecular geometry. PAPQMD performs the fitting between molecular mechanics and quantum mechanical energies considering all the perturbations that the modification in one geometric variable causes in all the others, enabling the parametrization even of large molecules. The ability of our method to reproduce experimentally derived force parameters is discussed and compared with the widely used Hopfinger's strategy. The study of the behavior of PAPQMD and Hopfinger's strategies for reproducing the force parameters of two complex molecules demonstrates the superiority of the methodology present

ISSN:0192-8651    

DOI:10.1002/jcc.540120603

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractHeats of formation (ΔHf) and proton affinities (PA) of 2‐, 3‐, and 4‐monosubstituted pyridines in the gas phase are calculated using the AM1 and PM3 semiempirical methods. The following substitutents are considered: NO2, CN, CF3, CHO, F, Cl, COCH3, H, CH3, OCH3, SCH3, NH2, and N(CH3)2. The results are compared with the experimental data. Both methods reproduce the ΔHfwith comparble accuracy; the rms deviations are 4.1 (AM1) and 4.5 kcal/mol (PM3) for the free bases and 9.5 (AM1) and 9.7 kcal/mol (PM3) for their conjugated acids. The PA are systematically underestimated by both methods, but AM1 appears to be clearly better than PM3 for reproducing the experimental values. The rms deviations for AM1 and PM3 are 5.1 and 9.6 kcal/mol, respectively. This is due to a cancellation of systematic errors in the calculated ΔHfin the AM1 case and to a summation of the errors in the PM3 case. Both methods correctly reproduce conformations of the molecules under consi

ISSN:0192-8651    

DOI:10.1002/jcc.540120604

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractAn atomic parametrization for the determination of a hydrophobicity index that depends on the molecular conformation is presented. The hydrophobicity parameter was calculated in four alternative ways based on charge densities and atomic contributions to the total molecular surface area and depending on the approach, the molecular dipole moment. The geometries required for the computations were calculated using quantum mechanical semiempirical methods as well as molecular mechanics. The charges were computed using semiempirical methods as well as the Gasteiger method.

ISSN:0192-8651    

DOI:10.1002/jcc.540120605

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractThis article presents theoretical calculations on bond energies for the first‐row diatomics C2, CN, CO, CF, N2, NO, NF, O2, FO, and F2, which vary in bond order from one to three. The atomic‐centered basis functions are systematically augmented with bond functions (BFs), which range in composition from (sp) to 2(spd), to determine the basis set which yields a dissociation energy closest to the experimentalDe. A strong correlation is found to exist between the bond order and the number of BFs required in the optimum basis set. Based on these results, we are able to predict the optimum composition of the BF basis which should be added to a DZP‐quality AO basis set for a case in which only the bond order is known. These optimized BF basis sets are shown in the accompanying article to give more accurate potential curves than larger basis sets without bond func

ISSN:0192-8651    

DOI:10.1002/jcc.540120606

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractIn the current practice of quantum chemistry, it is not clear whether corrections for basis set superposition errors should be applied to the calculation of potential energy curves, in order to improve agreement with experimental data. To examine this question, spectroscopic parameters derived from theoretical potential curves are reported for the homonuclear diatomics C2, N2, O2, and F2, using a configuration interaction method. Three different basis sets were used, including double zeta plus polarization, triple zeta plus double polarization, and double zeta polarization augmented by bond functions. The bond function basis sets, which were optimized in the preceding paper to obtain accurate dissociation energies, also gave the most accurate parameters. The potential curves were then corrected for basis set superposition error using the counterpoise correction, and the spectroscopic parameters were computed again. The BSSE‐corrected curves showed worse agreement with experiment for all properties than the original (uncorrected) curves. The reasons for this finding are discussed. In addition to the numerical results, some problems in the application of the BSSE correction to basis sets containing bond functions are shown. In particular, there is an overcounting of the lowering due to the bond functions, regardless of which type of correction is applied. Also, genuine BSSE affects cannot be separated from energy‐lowering effects due to basis set incompleteness, and we postulate that it is the latter which is strongly dominant in the calculation of covalent potential curves. Based on these arguments, two conclusions follow: (1) application of BSSE corrections to potential curves should not be routinely applied in situations where the bonding is strong, and (2) appropriate use of bond functions can lead to systematic improvement in the quality of potential cur

ISSN:0192-8651    

DOI:10.1002/jcc.540120607

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe molecular electrostatic potential is an important property for characterizing chemical reactivity and the interactions between biomolecules. A joint description of the molecular electrostatics and the molecular shape in 3‐space is more complete than the one provided by only the electrostatics. The characterization of the interrelations between the shape features of a formal “molecular surface” and electrostatic potential is of importance in assessing the degree of similarity within a family of molecules. In this work, we have applied a recently developed topological technique to characterize these aspects of the molecular shape. The approach allows one to calculate simple and concise shape codes which can be used for rationalizing structure‐activity correlations. These shape codes are related to topological invariants which characterize the topological structure given to the molecular surface by the electrostatic potential. In this work the molecules of interest are a series of four agonists of the H2‐receptor of histamine with very different pharmacological activities. We have analyzed the electrostatics on the fused‐sphere (van der Waals) surfaces of these compounds for a number of conformations. Some structural properties and the shape descriptions have been found to correlate with the activity. The results are discussed in the context of the current H2‐re

ISSN:0192-8651    

DOI:10.1002/jcc.540120608

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe empirical energy parameters for a calcium ion and its ligands in proteins were determined within a pairwise additive framework. The interaction energies of Ca2+‐water, Ca2+‐peptide group and Ca2+‐carboxyl group systems were calculated using theab initiomolecular orbital method with basis sets of double zeta quality including polarization or diffuse functions. The resulting potential energy surfaces served as references for the determination of the nonbonded parameters in the empirical energy function. The nonadditive corrections for the Ca2+‐ligand pair potentials are incorporated implicitly in the nonbonded paremeters by treating three‐body (1:2 complex) or seven‐body (1:6 complex) systems in reference calculations. Ligand polarizations induced by Ca2+are estimated from the partial atomic charges of two‐body (1:1 complex) systems. The charge sets were determined by scaling so as to reproduce the reference potential energy surfaces. The newly determined parameter set was used in a stochastic boundary molecular dynamics simulation of phospholipase A2. The solvated structure of the Ca2+‐binding site obtained from an X‐ray crystallographic study is well reproduced by

ISSN:0192-8651    

DOI:10.1002/jcc.540120609

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe harmonic molecular force fields for the nucleic acid bases, cytosine, and guanine, that have been previously published by several investigators are tested by the calculation of the relative intensities of the in‐plane modes in the ultraviolet resonance Raman (UVRR) effect from the two lowest lying absorption bands using a theoretical approach devised previously.1–3Since only a fraction of the 2N– 3 in‐plane vibrations of a molecule are active in the UVRR, the two criteria that are taken for the adjustment of the force constant are: (1) the closest possible agreement between the observed and calculated frequencies of the 2N– 3 in‐plane vibrations, and (2) the closest possible agreement between the calculated and observed intensities of those few vibrations that are strongly active in the ultraviolet resonance Raman effect. In particular it is necessary that the force constants be adjusted to avoid the calculation of intense Raman lines with frequencies that are not observed in the UVRR spectrum. Using this criteria, a new force field has been developed that appears to give better agreement with the observed UVRR intensities than previously published ones. It is suggested that this calculation of the UVRR intensities can be used to refine molecular force fields in combination with other methods such as isotopic replacement currently in use to refine forc

ISSN:0192-8651    

DOI:10.1002/jcc.540120610

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY

摘要:

AbstractThe C‐C glycol bond rotational energy in ethylene diacetate as a polyester model was compared using the semiempirical method AM1 and anab initiomethod with an STO‐3G basis set. The results were qualitatively much different depending on the method used.Ab initiocalculations showed the expected minima at 180 and near 60 (69.6) degrees dihedral angle with maxima at 0 and 120 degrees. The AM1 rotational curve indicated an apparent minimum at a 90 degree dihedral angle, a shallow, apparent maximum at 180 degrees and an apparent maximum at 0 degrees which could not be confirmed as minima or maxima via frequency calculations. Ethylene diacetate analog compounds with one or two ester oxygens replacing methylene group(s) gave curves with AM1 having the general shape for ethylene diacetate by theab initiomethod, indicating a parameterization problem for the otherwise very useful AM1 to correctly handle a compound with only two carbons between the two electronegative oxygen atoms thus rendering this method currently unsuitable for examination of rotational energy barriers of such polyester model compou

ISSN:0192-8651    

DOI:10.1002/jcc.540120611

出版商:John Wiley&Sons, Inc.    

年代:1991

数据来源: WILEY