Journal of Computational Chemistry

Freyberg, Berthold Von; Braun, Werner

doi: 10.1002/jcc.540140503pmid: N/A

We present analytical expressions to calculate the gradient of the water‐accessible surface area of proteins with respect to Cartesian coordinates and dihedral angles. A detailed mathematical analysis leads to corrected equations for the gradient calculation used previously in the ANAREA program. To study the hydrophobic effect of solvent‐protein interactions, our expressions have been implemented to further improve the program package FANTOM. We used this version of FANTOM to minimize the ECEPP/2 and the hydrophobic energy of tendamistat. © 1993 John Wiley & Sons, Inc.

Wang, Peng; Zhang, Yala; Glaser, Rainer; Streitwieser, Andrew; Schleyer, Paul von R.

doi: 10.1002/jcc.540140504pmid: N/A

Geometry optimizations at the HF/3‐21G(*) and HF/6‐31G* levels of ab initio theory have been carried out for various isomers of model disubstituted phosphoranes PH3XY(X, YOH, CH3, NH2, and SH). Reasonable agreement was obtained between the optimized geometries and available crystal structure data for analogous compounds. The isomers were further characterized by frequency calculations. The MP2/6‐31G*//6‐31G* + ZPE energy data reveal that the interactions between the ligands are relatively small (0–4 kcal mol−1) for the most stable conformations of the isomers. Hence, for these conformations the apicophilicities (based upon monosubstituted phosphoranes) are approximately additive. The less stable PH3XY conformations are in general transition states or higher‐order saddle points, and their interligand interactions are larger in magnitude (up to 10 kcal mol−1); the results with these conformations suggest that apicophilicities may not be as additive for some highly substituted phosphoranes. © 1993 John Wiley & Sons, Inc.

Alkorta, Ibon; Villar, Hugo O.; Arteca, Gustavo A.

doi: 10.1002/jcc.540140505pmid: N/A

The electrostatic potentials of 21 molecules containing different functional groups has been computed at the ab initio RHF/6‐31G* level on a series of solvent accessible surfaces and compared with MNDO, AM1, and PM3‐derived pontentials. We analyzed in detail the distribution of electrostatic potentials on the surfaces around their maximum and minimum values and found out that consistently MNDO gives results similar to ab initio potentials. The actual values of the MNDO electrostatic potentials show a systematic deviation from the “correct” results, but the pattern of the MEP distribution on the surface is similar to that of the ab initio results. In contrast, PM3 fails in some cases to give even the correct number or distribution of “hot spots” of potential (low MEP) on the surface. AM1 behaves somewhere between these two semiempirical methods. As a conclusion, MNDO would be suggested as the best approach to analyses requiring a fast and efficient mapping of electrostatic potentials on simplified models of molecular surfaces. © 1993 John Wiley & Sons, Inc.

Bass, Michael B.; Ornstein, Rick L.

doi: 10.1002/jcc.540140506pmid: N/A

In our earlier molecular dynamics simulations, we found that there was a discrepancy between the predicted and experimental product ratios when norcamphor is hydroxylated by cytochrome P450cam. The experimental results suggest that there is a nearly equimolar ratio between the 5‐ and 6‐hydroxynorcamphor (45% 5‐, 47% 6‐, and 8% 3‐hydroxynorcamphor) (W.M. Atkins and S.J. Sligar, J. Am. Chem. Soc., 109, 3754 (1987)). Our previous simulations predicted predominately from 68–88% 5‐hydroxynorcamphor (M.B. Bass et al., Prot. Struct. Funct. Genet., 13, 26 (1992); M.B. Bass et al., Proc. Natl. Acad. Sci. U.S.A., submitted). One possible explanation for this discrepancy is that the simulations were performed using D‐norcamphor while the experiments were conducted with racemic norcamphor. The suggestion that norcamphor is the D‐isomer was based upon the similarity with the native substrate D‐camphor. Indeed, the reported crystallographic structure for norcamphor‐bound P450cam models norcamphor as the D‐isomer. Unfortunately, the two stereomers have never been separated. The simulations presented here model the L‐isomer of norcamphor. Three simulations each of the L‐ and D‐isomers of norcamphor bound to cytochrome P450cam were compared to account for the effects due to substrate orientation and the assignment of random velocities. The results presented here show that the L‐isomer of norcamphor is predicted to give rise to predominately 6‐hydroxynorcamphor, while the D‐isomer gives rise to mainly 5‐hydroxynorcamphor. From this data, we infer that racemic norcamphor will give rise to nonracemic 5‐ and 6‐hydroxynorcamphors after oxidation by cytochrome P450cam. © 1993 John Wiley & Sons, Inc.

Zhou, Taijin

doi: 10.1002/jcc.540140507pmid: N/A

By using the group symmetrical localized molecular orbitals (SLMOs) as configuration‐generating orbitals (CGOs) of many‐electron wave functions, the symmetry adaptation of many‐electron spaces is greatly simplified, and novel orthogonal bonded functions (OBFs), as complete space‐ and spin‐adapted antisymmetrized products, are introduced. The corresponding programs for the solutions of OBFs are developed. © 1993 John Wiley & Sons, Inc.

Zheng, Qiang; Rosenfeld, Rakefet; Vajda, Sandor; Delisi, Charles

doi: 10.1002/jcc.540140508pmid: N/A

We describe, test, and apply a new computational algorithm for generating protein loop conformations subject to distance and secondary structure constraints. The algorithm is based upon initial scaling and subsequent relaxation of covalent bond lengths. The scaling‐relaxation procedure needs no additional energy terms and can be readily incorporated into existing molecular modeling packages. The algorithm uses an all‐atom energy function from the outset in a straightforward way so that about 60% of the generated loop conformations are free of severe distortions of covalent bond lengths and angles. An extensive application to the major loop conformations of TFIIIA‐type zinc fingers (Zif268 and ADR1) is presented, as well as preliminary calculations on hypervariable loops of two immunoglobulins (MCPC603 and Bence‐Jones). © 1993 John Wiley & Sons, Inc.

Schwegler, Eric; Kozlowski, Pawel M.; Adamowicz, Ludwik

doi: 10.1002/jcc.540140509pmid: N/A

The electronic energy of atoms and molecules may be evaluated accurately by the use of wave functions where the interelectronic distances are explicitly present. In particular, explicitly correlated Gaussian‐type functions make these types of calculations feasible and computationally tractable even for more extended systems. The resulting multielectron integrals may be reduced to standard one‐ and two‐electron integrals that are readily evaluated. Initial calculations have been made for the Be atom where all four electrons were correlated at the same time. The preliminary results show that accurate results may be obtained. © 1993 John Wiley & Sons, Inc.

Alkorta, Ibon; Villar, Hugo O.; Cachau, Raul E.

doi: 10.1002/jcc.540140510pmid: N/A

A conformational study of the 2,3,6,7‐tetrahydroazepine (THA) and closely related systems has been carried out using MM3 and CHARMm molecular mechanics, AM1 semiempirical, as well as Hartree‐Fock and local density functional (LDF) ab initio methods. For THA, all methods give similar optimal geometries; however, only MM3 agrees with the Hartree‐Fock calculations using a 6‐31G* basis set and LDF in the rank order of energies and nature of the stationary points characterized. AM1 shows serious disagreements with those results. Tetrahydrobenzazepines and a D1 receptor agonist containing the THA nucleus were studied using CHARMm, MM3, and AM1 calculations. All methods provide similar descriptions of the geometries of the conformations accessible to these compounds. However, the same disparities in the rank order of energies are observed. © 1993 John Wiley & Sons, Inc.