摘要:

AbstractThe program AQUARIUS2 calculates probable positions for water molecules within the first hydration shell of any protein for which atomic coordinates are known. Like its predecessor, AQUARIUS, it uses a knowledge of water molecules sites from crystallographically determined protein structures. Energy calculations are not employed. It differs substantially from the original program in that a 3‐D probability map (for solvent sites) is generated around the surface of the protein instead of the previously used discrete points. The accuracy of the program has been gauged by comparison with experimentally derived water molecule positions for proteins not used in the knowledge base of the program. It has also been tested by combining the probability density maps with crystallographically determined electron density maps for the protein porphobilinogen deaminase. This procedure filters the most likely solvent electron density peaks from the background noise and has been used in the determination of the solvent structure around the protein nerve growth factor. © John Wiley&Sons, I

ISSN:0192-8651    

DOI:10.1002/jcc.540140902

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractEstimating logP(logarithm of “1‐octanol to water” partition coefficients) as a measure of lipophilicity for organic compounds is of considerable importance in drug discovery. Several methods have been developed for this purpose, each with its own drawbacks and advantages. In this article, a systematic comparison of three well‐documented and fully computerized methods has been attempted for a set of nucleosides and bases. The first method (BLOGP) is based on overall molecular properties derived from a molecular orbital calculation to predict logP. The second method (CLOGP) uses fragmental lipophilicity constants with correction factors and treats logPas an additive‐constitutive property. The third method (ALOGP) is based on an additivity scheme of atomic lipophilicity constants, with the constitutive factor governed by an elaborate list of atom types. However, none of these methods take into account conformational flexibility or intramolecular hydrogen bonding, which can cause substantial discrepancy between observations and predictions. A comparison of predictions from each of these methods indicates that the atomic contribution method (ALOGP withr= 0.842 and SD = 0.51) is better than other methods (withr= 0.395 and SD = 1.2 for BLOGP andr= 0.713 and SD = 0.93 for CLOGP) for this class of compounds. Our overall assessment is that we do not have, as yet, a highly reliable, fully computerized logPprediction method applicable to flexible heterocycles such as nucleoside analogs. © John Wiley

ISSN:0192-8651    

DOI:10.1002/jcc.540140903

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThree hydrogen‐bonded minima on the phenol‐water, C6H5OH—H2O, potential energy surface were located with 3–21G and 6–31G** basis sets at both Hartree–Fock and MP2 levels of theory. MP2 binding energies were computed using large “correlation consistent” basis sets that included extra diffuse functions on all atoms. An estimate of the effect of expanding the basis set to the triple‐zeta level (multipleffunctions on carbon and oxygen and multipledfunctions on hydrogen) was derived from calculations on a related prototype system. The best estimates of the electronic binding energies for the three minima are –7.8, –5.0, and –2.0 kcal/mol. The consequences of uncertainties in the geometries and limitations in the level of correlation recovery are analyzed. It is suggested that our best estimates will likely underestimate the complete basis set, full CI values by 0.1–0.3 kcal/mol. Vibrational normal modes were determined for all three minima, including an MP2/6–31G** analysis for the most strongly bound complex. Computational strategies for larger phenol–water complexes are disc

ISSN:0192-8651    

DOI:10.1002/jcc.540140904

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractNet atomic charges are derived from a least‐squares fitting to electrostatic potentials at atomic sites. The method treats atoms in the molecule as having spherically averaged Hartree–Fock densities, the atomic densities overlapping with one another. The method has the advantage of best reproducing the electrostatic potentials at the atomic nuclei and avoiding the arbitrariness in choosing the points used in the fitting. We have written a FORTRAN program, CHELPN92 (Z. Su, Chemistry Department, SUNY at Buffalo, Buffalo, NY, 1992), based on the method and applied it to deuterated benzene,l‐alanine,d,l‐histidine, 2‐methyl‐4‐nitroaniline, and deuterated pyridinium‐1‐dicyanomethylide using the molecular geometry and electrostatic potentials from analysis of accurate X‐ray diffraction data. The derived charges are used to calculate the molecular dipole moments. While the charges from this method are in general significantly different from those from the kappa refinement [P. Coppens, T.N. Guru Row, P. Leung, E.D. Stevens, P.J. Becker, and Y.W. Yang,Acta Cryst. A,35, 63 (1979)], the dipole moments obtained with the new method agree well with those from the kappa refinement. ©

ISSN:0192-8651    

DOI:10.1002/jcc.540140905

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractA new, generalized, method for measuring the steric size of ligands and substituents has been developed. The method is based on the solid angle concept, the solid angle being generated by the pairwise addition of spheres (atoms). The problem of overlapping spheres (atoms) has been solved analytically and the algorithm provided permits evaluation of the steric space occupied by any combination of spheres (atoms). A range of solid angles for commonly encountered ligands and substituents has been determined and compared to literature values for linear cone angles. © John Wiley&Sons, Inc

ISSN:0192-8651    

DOI:10.1002/jcc.540140906

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractSeveral methods are available in the literature for the conformational analysis of small molecules. Each of these methods has some advantages and some disadvantages. Also, each of these methods may be expected to perform better or worse on different types of molecules. There is no clear calibration of each of these methods against a “standardized” set of molecules available in the literature. Such a reference work would be useful to the community because it would allow the choice of methods to be based on some facts. We attempted to provide a start to such a calibration in this article with an examination of the SYBYL SEARCH method. Methods for evaluating the performance of this method are described in detail and will be applied to all other available conformational analysis methods in future papers. © John Wiley&Sons,

ISSN:0192-8651    

DOI:10.1002/jcc.540140907

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractThe nonbonded portion of a force field for lecithins was characterized by application to the study of the crystal packing geometry and energetics of eight different molecules. The molecules were either lecithin fragments or chosen to isolate particular intermolecular features to test the accuracy of the force field specifically for those interactions. In particular, the hydrocarbon interactions, hydrogen bonding, electrostatics, and phosphate interactions were critiqued. The results support previous findings that indicated that this force field is reasonably accurate for lecithins. For all molecules, a minimum was found near the experimentally determined crystal structure. Using D‐glucitol as an example, it is shown that the structural effect of hydrogen bonding is better represented by a nonelectrostatic force‐field model than by a purely electrostatic model. Results obtained with glycerylphosphocholine and four smaller organic phosphate molecules suggest that further study of nonbonded interactions of phosphate groups is needed. © John Wiley&Sons,

ISSN:0192-8651    

DOI:10.1002/jcc.540140908

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractNew combining rules are proposed for the well depth, ϵ, and interaction distance, σ, describing nonbonded interatomic forces for rare gas pair interactions. Concepts underlying current combining rules applied in simulations of macromolecular and polymer systems are shown to be incompatible with experimental data on the rare gases. The current combining rules are compared with the new results using the experimental data. Mathematical properties of combining rules are considered, and it is shown how to reduce combining rule formulas from a two‐parameter to a single‐parameter problem. It is also shown how to graphically analyze combining rules against experimental data. We demonstrate using this analysis technique that the rare gas potentials do not obey a single combining rule for the ϵ parameter but do follow a single combining rule for the σ parameter. Finally, we demonstrate that a combining rule using both ϵ and ω can be used to predict the ϵ parameters for the mixed rare gas pairs. © John Wile

ISSN:0192-8651    

DOI:10.1002/jcc.540140909

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractA comparison is made between geometry optimization in Cartesian coordinates, using an appropriate initial Hessian, and natural internal coordinates. Results on 33 different molecules covering a wide range of symmetries and structural types demonstrate that both coordinate systems are of comparable efficiency. There is a marked tendency for natural internals to converge to global minima whereas Cartesian optimizations converge to the local minimum closest to the starting geometry. Because they can now be generated automatically from input Cartesians, natural internals are to be preferred overZ‐matrix coordinates. General optimization strategies using internal coordinates and/or Cartesians are discussed for both unconstrained and constrained optimization. © John Wiley&Sons, I

ISSN:0192-8651    

DOI:10.1002/jcc.540140910

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY

摘要:

AbstractA new approach to the computation of molecular electrostatic potentials based on the AM1 wave function is described. In contrast to the prevailing philosophy, but consistent with the underlying NDDO approximation, no deorthogonalization of the wave function is carried out. The integrals required for the computation of the electronic contributions to the molecular electrostatic potential are evaluated in a manner similar to that of the AM1 core‐electron attraction integrals, while the nuclear contributions are computed using a new semiempirical function—ZA(SASA,SpSp)[1 + exp[ – ωA(RAi– δA)]]—where the atomic parameters ωAand δAare obtained by calibration against the results ofab initioHF/6‐31G* calculations. Isopotential contour maps for guanine and cytosine obtained with the new method are qualitatively almost indistinguishable from their HF/6‐31G* counterparts, while quantitative comparisons for the minima for a wide range of molecules are reproduced with an rms error of 5.2 kcal mol−1. The locations of the “lone‐pair” minima for a wide range of heterosubstituted organic molecules generally fall within 0.02 Å of the corresponding HF/6‐31G* minima while those in the π‐regions of unsaturated molecules are generally within 0.2 Å. Because of the rapid integral evaluation, the fully semiempirical method described here is extremely economical. For example, for the guanine–cytosine base pair it is>500 times faster than calculations in which the complete integral matrix is computed analytically from the deorthogonalized AM1 wav

ISSN:0192-8651    

DOI:10.1002/jcc.540140911

出版商:John Wiley&Sons, Inc.    

年代:1993

数据来源: WILEY