Ab initio Molecular Electrostatic Potential Grid Maps for Quantitative Similarity Calculations of Organic Compounds

The program MolSim designed to calculate the similarity of different molecules quantitatively in a fast and easy way is described. The molecular similarity is estimated for the molecular shape as well as for the electrostatic potentials of the molecules derived from ab initio calculations. A grid-based method is used to determine the steric and electrostatic similarities between a lead compound and the corresponding test set by calculating the Spearman correlation coefficient. The superpositioning of the molecules was accomplished with the SEAL algorithm incorporating a Monte Carlo simulated annealing approach while preserving the conformational flexibility of the calculated structures.The ability of the program was tested on a set of Sandalwood odour compounds, a class of substances that is difficult to analyse with respect to its structure-activity relationship because of the structural diversity of Sandalwood odour compounds, in contrast to their high selectivity and pronounced structural specificity. The application of the program on a small test set of these compounds showed that the program is able to explain the Sandalwood odour activity correctly.Electronic Supplementary Material available.     

Optimization of parameters for semiempirical methods IV: extension of MNDO,AM1, and PM3 to more main group elements

The NDDO semiempirical methods MNDO, AM1, and PM3 have been extended to all the remaining non-radioactive elements of the main group, excluding the noble gases. Most of the new elements are of Groups I and II. 44 sets of parameters are presented for the following methods and elements. MNDO: Na, Mg, K, Ca, Ga, As, Se, Rb, Sr, In, Sb, Te, Cs, Ba, Tl, and Bi; AM1: Li, Be, Na, Mg, K, Ca, Ga, As, Se, Rb, Sr, In, Sn, Sb, Te, Cs, Ba, Tl, Pb, and Bi; PM3: B, Na, K, Ca, Rb, Sr, Cs, and Ba. Average errors are presented for heats of formation, molecular geometries, etc.     

Comparison of the accuracy of semiempirical and some DFT methods for predicting heats of formation

A comparison is made of the relative accuracy of some NDDO semiempirical methods and the DFT functionals LYP and PW91 using both double and triple zeta basis sets. The comparison is between the calculated heat of formation and that reported in the NIST database.Electronic Supplementary Material Parameters for the tailored method are available in the supplementary material; these are suitable for use with MOPAC2002. All raw data (experimental heats of formation, geometries, total energies and heats of formation for the various methods, etc.) are also provided in CAChe format. Supplementary material is available for this article if you access the article at . A link in the frame on the left on that page takes you directly to the supplementary material.     

The Interplay of Angle Strain and Aromaticity: Molecular and Electronic Structures of [0n]Paracyclophanes

The belt-like polyphenylenes, [0_n]paracyclophanes, (n = 5 and 6), have been investigated using semi-empirical, ab initio and DFT methods. The molecular structure, rotational barrier on twisting a single phenyl ring and the aromatic character within each ring as well as in the whole molecule have been evaluated. [0₅]Paracyclophane is predicted to have a quinonoid structure. In contrast, the equatorial pentaphenyl fragment found in C₇₀ as well as the hexagons of the less strained [0₆]paracyclophane have benzenoid character. Approximate band structures have been derived for larger cycles of [0_n] paracyclophanes.Electronic Supplementary Material available.     

Electrostatic properties deduced from refined structures of NADH-cytochrome b5 reductase and the other flavin-dependent reductases: Pyridine nucleotide-binding and interaction with an electron-transfer partner

Electrostatic properties on the protein surface were examined on the basis of the crystal structure of NADH-cytochrome b₅ reductase refined to a crystallographic R factor of 0.223 at 2.1 Å resolution and of the other three flavin-dependent reductases. A structural comparison of NADH-cytochrome b₅ reductase with the other flavin-dependent reductases, ferredoxin-NADP⁺ reductase, phthalate dioxygenase reductase, and nitrate reductase, showed that the α/β structure is the common motif for binding pyridine nucleotide. Although the amino acid residues associated with pyridine nucleotide-binding are not conserved, the electrostatic properties and the location of the pyridine nucleotide-binding pockets of NADH-requiring reductases were similar to each other. The electrostatic potential of the surface near the flavin-protruding side (dimethylbenzene end of the flavin ring) of NADH-cytochrome b₅ reductase was positive over a wide area while that of the surface near the heme-binding site of cytochrome b₅ was negative. This implied that the flavin-protruding side of NADH-cytochrome b₅ reductase is suitable for interacting with its electron-transfer partner, cytochrome b₅. This positive potential area is conserved among four flavin-dependent reductases. A comparison of the electron-transfer partners of four flavin-dependent reductases showed that there are significant differences in the distribution of electrostatic potential between inter-molecular and inter-domain electron-transfer reactions. © 1996 Wiley-Liss, Inc.