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In molecular rotors, a type of molecular machine, spontaneous rotors without the need for an external stimulus are promising because conventional molecular rotors require a continuous energy supply. In this study, we demonstrate spontaneous transformation from kinetically favored metastable right-handed helical aggregates to thermodynamically stable left-handed helical aggregates after an evaporation procedure. In addition, we propose the conditions for preparation of metastable right-handed helical aggregates, whose chirality can be spontaneously inverted, based on kinetic analysis. This molecular power spring will be useful for designing new types of molecular machines.

The canonical molecular orbitals (CMO) calculation provides useful knowledge such as molecular orbitals, energy level, charge density and so on. As one of the properties obtained from the CMO calculation of protein results, the interaction energy analysis between amino acid residues and/or substrates is useful as molecular design and functional analysis. The energy decomposition analysis approaches are the well-known calculation methods for interaction energy analysis, however, the electronic structure calculation of large molecule is very expensive and hard to achieve. Therefore, we have implemented the interaction analysis method by using the energy density analysis (EDA) method. The calculation for the EDA method is as simple as the Mulliken population method but requires matrix elements for energy calculation. By adopting the grid-free method for the exchange-correlation term, we could apply the EDA method in the DFT scheme.

Streptomyces incarnatus NRRL8089 produces the antiviral, antifungal, antiprotozoal nucleoside antibiotic sinefungin. To enhance sinefungin production, multiple mutations were introduced to the rpoB gene encoding RNA polymerase (RNAP) β-subunit at the target residues, D447, S453, H457, and R460. Sparse regression analysis using elastic-net lasso-ridge penalties on previously reported H457X mutations identified a numeric parameter set, which suggested that H457R/Y/F may cause production enhancement. H457R/R460C mutation successfully enhanced the sinefungin production by 3-fold, while other groups of mutations, such as D447G/R460C or D447G/H457Y, made moderate or even negative effects. To identify why the rif cluster residues have diverse effects on sinefungin production, an RNAP/DNA/mRNA complex model was constructed by homology modeling and molecular dynamics simulation. The 4 residues were located near the mRNA strand. Density functional theory–based calculation suggested that D447, H457, and R460 are in direct contact with ribonucleotide, and partially positive charges are induced by negatively charged chain of mRNA.

Although canonical molecular orbital (CMO) calculations for proteins are very useful for protein engineering, they are computationally expensive and difficult to achieve because proteins are large molecules. We had developed the third-generation density functional (3G DF) method, which performed electronic state calculation with high efficiency in parallel computer by performing only matrix operation during the SCF calculation. In this study, by applying the powerful computing platform of graphic processing unit (GPU) to our 3G DF calculation method, we constructed a computing environment that achieved the large-scale CMO computation with high efficiency.Although canonical molecular orbital (CMO) calculations for proteins are very useful for protein engineering, they are computationally expensive and difficult to achieve because proteins are large molecules. We had developed the third-generation density functional (3G DF) method, which performed electronic state calculation with high efficiency in parallel computer by performing only matrix operation during the SCF calculation. In this study, by applying the powerful computing platform of graphic processing unit (GPU) to our 3G DF calculation method, we constructed a computing environment that achieved the large-scale CMO computation with high efficiency.

Recently, hole mobilities in polyethylene (PE) oligomers has been investigated by means of Marcus theory. Although it is well known that Marcus theory is successfully applied to various organic semiconductors, strictly speaking, charge transfer in organic molecules requires quantum mechanical treatment to account for quantum nuclear tunneling between vibrational levels. We evaluate hole transfer rates between PE oligomers by Fermi's golden rule (FGR) rate expression and by classical Marcus rate expression at various temperature and energetic disorder. The results indicate that Marcus theory can be a good approximation for describing hole transfer between long polyethylene chain with small reorganization energy or in highly energetically disordered system. However, hole hopping rate between C10H22 molecules computed by Marcus theory was roughly 100 times smaller than that computed through FGR rate expression. High-temperature approximation must be applied with caution especially for quantitative evaluation of hole transfer rates in PE.

Hole mobility in crystalline polyethylene (PE) is evaluated from an atomistic point of view, with the combination of quantum chemical calculation and kinetic Monte Carlo simulations. Hole hopping rate between PE chains are computed by Fermi’s golden rule and Marcus rate expression. It turns out that hole transfer in PE occurs in a hopping regime rather than in a band regime even for crystalline structure without any inherent structural disorders. The results indicate that in crystalline PE, hole hops between localized states that are created by polaronic effect. The hole mobility is strongly dependent on the chain length, and increases with increasing chain-length. When the chain length was comparable to the thickness of lamellar crystals, i.e., the characteristic length scale of crystal in the direction of c axis, hole mobility and activation energy for hole transfer were in reasonable agreement with experimental values. Simulated results support the experimental prediction that fast and slow mobility are due to charge transfer in the crystalline region and amorphous region, respectively. Our findings show that high hole mobility observed in crystalline PE, regardless of the small inter-molecular electronic couplings, is due to the small reorganization energy, which is realized through the intra-molecular hole delocalization, and due to quantum tunneling effects owing to the small energetic disorder and high-frequency intra-molecular phonon modes.

In recent years, excess electron transfer in organic liquids has attracted increasing interest owing to the emerging class of liquid organic semiconductors. In this study, to achieve a comprehensive understanding of electron conduction in liquids, we investigate hopping electron conduction in liquids from an atomistic viewpoint. High-pressure liquid benzene is chosen as a simple model system. Hopping electron mobility is computed using a combination of molecular dynamics simulations, quantum chemical calculations, and kinetic Monte Carlo methods. The computed electron mobility is in good agreement with the experimental values. Because the amplitude of the intermolecular vibration observed in liquids is larger compared to that in solids, the effect of dynamic disorder on electron mobility is investigated. The time scale of the change in electronic couplings due to the rotation of molecules is comparable to that of the electron residence time at each benzene molecule at the absence of change in the arrangem...

Fast transient current in polymeric insulator is widely interpreted in terms of semi-phenomenological Scher-Montroll (S-M) theory, owing to the somewhat satisfactory fitting to the experimental data. However, from a theoretical point of view, it is questionable whether this model can be applied to carrier transfer in insulators where polaronic effect plays an important role. In this contribution, hole transfer in amorphous polyethylene (PE) is simulated with the combination of molecular dynamics, quantum chemical, and kinetic Monte Carlo calculations, without adopting semi-empirical or phenomenological models. Hole hopping rates were computed with the approximate form of the Fermi's golden rule rate kernel that takes into account the coupling between carriers and molecular vibrational modes. Current waveforms were computed from the trajectories of holes. Computed current waveforms exhibit the so called anomalous diffusion properties, and moreover, they indeed roughly obey the well-known “universality” predicted by S-M theory. It is also shown that, in line with experimental findings, the slopes of the S-M plot deviates from the prediction of S-M theory.

Carrier conduction and injection properties in organic liquid insulator is investigated from an atomistic point of view. «-hexane is chosen as a simple model. Hole mobilities in n-hexane is computed with molecular dynamics, quantum chemical and kinetic Monte Carlo calculations. Hole injection current is computed via semi-phenomenological models with the aid of quantum chemical calculations. At low electric field, hole mobility is comparable to that of ions, however, in electric fields approaching the dielectric breakdown field, hole mobility becomes larger than that of ions. As pointed out for charge injection in organic semiconductors, the success of F-N model is probably accidental because the thickness of the potential barrier is larger than the distance between hopping sites. The injection current rapidly increases with the electric field above 102 kV/mm.

The canonical molecular orbital (CMO) calculation can help to understand chemical properties and reactions in proteins. However, it is difficult to perform the CMO calculation of proteins because of its self-consistent field (SCF) convergence problem and expensive computational cost. To certainly obtain the CMO of proteins, we work in research and development of high-performance CMO applications and perform experimental studies. We have proposed the third-generation density-functional calculation method of calculating the SCF, which is more advanced than the FILE and direct method. Our method is based on Cholesky decomposition for two-electron integrals calculation and the modified grid-free method for the pure-XC term evaluation. By using the third-generation density-functional calculation method, the Coulomb, the Fock-exchange, and the pure-XC terms can be given by simple linear algebraic procedure in the SCF loop. Therefore, we can expect to get a good parallel performance in solving the SCF problem by using a well-optimized linear algebra library such as BLAS on the distributed memory parallel computers. The third-generation density-functional calculation method is implemented to our program, ProteinDF. To achieve computing electronic structure of the large molecule, not only overcoming expensive computation cost and also good initial guess for safe SCF convergence are required. In order to prepare a precise initial guess for the macromolecular system, we have developed the quasi-canonical localized orbital (QCLO) method. The QCLO has the characteristics of both localized and canonical orbital in a certain region of the molecule. We have succeeded in the CMO calculations of proteins by using the QCLO method. For simplified and semi-automated calculation of the QCLO method, we have also developed a Python-based program, QCLObot.

This article reports the proton tautomerization effects of distal histidine residues in carbonmonoxy myoglobin according to the density functional calculations of the whole protein. The electron eigenstates and electrostatic potential (ESP) distributed around heme and its pocket vary significantly depending on the protonation positions of the distal histidine residues. To investigate the range over which the electronic structures are affected by the proton tautomerization, the quantum mechanics/molecular mechanics (QM/MM) method is applied to probe the QM size to reproduce the atomic partial charges and ESP around the active center. Consequently, we show that these properties converged for the 300 pm QM/MM system in this study. During the analysis, we also find that amino residues such as Phe43, Val68, and Phe138 interact strongly with heme through orbital mixing, indicating that the protein is a medium not only interacting with the reaction center, but also buffering on electrons. © 2013 Wiley Periodicals, Inc.

We applied the residual cutting (RC) method, which has excellent converging characteristics, as the numerical solution of elliptic partial differential equations, to the coupled perturbed (CP) equation. This method also shows robust and precise converging characteristics in solving the CP equation. For small molecules, it was as effective as the Pople method. As molecule size increases, the number of steps required to achieve convergence increases. For systems with large size of molecules, this method is shown to be more advantageous than the Pople method in convergence, required memory and the amount of calculation.

We investigate hopping electron conduction in liquids from an atomistic point of view, in order to achieve a comprehensive understanding of excess electron conduction in liquids. Liquid benzene is chosen as a simple model system. Hopping electron mobility is computed with the combination of molecular dynamics simulations, quantum chemical calculations, and kinetic Monte Carlo methods. The computed values of electronic couplings and reorganization energies suggest that excess electron transfer occurs in the hopping regime, as predicted by experiments and empirical models. The computed electron mobility is in good agreement with the experimental values over a wide range of temperatures and pressures.

We construct a wonderful compactification of the variety parameterizing n distinct labeled points in X away from D, where X is a nonsingular variety and D is a nonsingular proper subvariety. When D is empty, it coincides with the Fulton–MacPherson configuration space.

Japan Vietnam Petroleum Co., Ltd. (JVPC) discovered oil accumulations in the Lower Miocene sandstones and the fractured granitic basement at the Rang Dong structure in Block 15-2, offshore S.R. Vietnam in 1994 and started oil production in 1998, and phased-mannered field development has been implemented due to the uncertainty in reservoir extent and connectivity.The Lower Miocene Reservoir consists of thin alternations of sandstone and shale which is supposed to be deposited in marginal area between terrestrial and marine environment. As the field development proceeded, it became evident that reservoir quality differs more than expected. A major focus of reservoir management therefore has been to place new development wells in optimal locations in order to increase the well productivity of development wells. And as one of new technologies, geosteering technique was introduced.The keys to the success of the well placement are understanding of the field, preparation prior to drilling, continuous interpretation of the real-time data while drilling, integrated teamwork at the well-site and good communication with office for the fast and consented decision.In addition to these essentials, real-time resistivity image, which is newly introduced to JVPC together with standard LWD data, provided helpful information to understand “where and how we are drilling”. The well trajectory was modified on real-time if required based on the interpretation of these data, the correlation with offset wells and geological models.A series of wells have been drilled with this process and achieved significant improvement of well productivity.This paper demonstrates recent geosteering examples and the results in the Rang Dong Field.

馬心筋一酸化炭素ミオグロビン（MbCO）における，遠位ヒスチジン（HIS）イミダゾール基の水素の位置の違いによるヘムと配位子への電子構造の影響を調べるため，いくつかの活性中心モデルを用いて密度汎関数計算を実行した．遠位HISイミダゾール基の水素が一酸化炭素（CO）配位子側に向くe位に水素が付いたモデルでは，δ位に水素が付いたモデルに比べてヘム鉄-CO結合部位近傍の静電ポテンシャルが正に高く，準位が高いヘム鉄由来の被占コーン・シャム軌道準位が安定化した．水素の位置の違いは結合したCOにも影響を与えており，炭素のマリケン電荷の変化量は0.016に及んだ．MbCOにおいても，遠位HISとヘムおよび配位子との相互作用は大きく，配位子結合状態の記述には遠位HISを量子化学的にあらわに考慮する必要があることが示された．

An all-electron calculation on the non-symmetric insulin hexamer was successfully carried out using a precise initial guess of the combined quasi-canonical localized orbitals and the parallel density functional program employing the distributed matrices. The numbers of residues, atoms, and orbitals were 306, 4728, and 26 790, respectively. To our knowledge, insulin hexamer is the largest system calculated using the full-scale canonical density functional molecular orbital method. The calculation for the initial guess and the insulin hexamer took 26.5 h using 24 Xeon processors (3.2 GHz) and 65 h using 64 Itanium 2 processors (1.3 GHz), respectively.

We developed a new parallel density-functional canonical molecular-orbital program for large molecules based on the resolution of the identity method. In this study, all huge matrices were decomposed and saved to the distributed local memory. The routines of the analytical molecular integrals and numerical integrals of the exchange-correlation terms were parallelized using the single program multiple data method. A conventional linear algebra matrix library, ScaLAPACK, was used for matrix operations, such as diagonalization, multiplication, and inversion. Anderson's mixing method was adopted to accelerate the self-consistent field (SCF) convergence. Using this program, we calculated the canonical wavefunctions of a 306-residue protein, insulin hexamer (26,790 orbitals), and a 133-residue protein, interleukin (11,909 orbitals) by the direct-SCF method. In regard to insulin hexamer, the total parallelization efficiency of the first SCF iteration was estimated to be 82% using 64 Itanium 2 processors connected at 3.2 GB/s (SGI Altix3700), and the calculation successfully converged at the 17-th SCF iteration. By adopting the update method, the computational time of the first and the final SCF loops was 229 min and 156 min, respectively. The whole computational time including the calculation before the SCF loop was 2 days and 17 h. This study put the calculations of the canonical wavefunction of 30,000 orbitals to practical use. © 2007 Wiley Periodicals, Inc. J Comput Chem, 2007

Although degradation process of polymers is correlated with space charge, there remains a lack of understanding of charge transport phenomena and quantitative estimation of carrier mobility has not yet been accomplished. In this research, hole mobility in polyethylene (PE) is calculated by means of standard density functional theory. It turns out that hole transfer in PE occurs in a “hopping regime”. Moreover, estimated hole mobility is in reasonable agreement with experimental values. In addition, it is implied that the existence of carbonyl defect is likely to increase hole mobility which is consistent with experimental results at least for low density PE.

Oxygen tolerance of selenium-containing [NiFeSe] hydrogenases (Hases) is attributable to the high reducing power of the selenocysteine residue, which sustains the bimetallic Ni–Fe catalytic center in the large subunit. Genes encoding [NiFeSe] Hases are inherited by few sulphate-reducing δ-proteobacteria globally distributed under various anoxic conditions. Ancestral sequences of [NiFeSe] Hases were elucidated and their three-dimensional structures were recreated in silico using homology modelling and molecular dynamic simulation, which suggested that deep gas channels gradually developed in [NiFeSe] Hases under absolute anaerobic conditions, whereas the enzyme remained as a sealed edifice under environmental conditions of a higher oxygen exposure risk. The development of a gas cavity appears to be driven by non-synonymous mutations, which cause subtle conformational changes locally and distantly, even including highly conserved sequence regions.

We give a way to obtain formulas for …⁄ˆ k+1 in terms ofand ‚-classes where … : Mg;n+1 ! Mg;n(g = 0;1;2) by the localization theorem. By using the formulas, we obtain Kontsevich{ Manin type reconstruction theorems for M0;n(P m );M1;n; and M2;n. We also (re)produce a lot of well-known relations in tautologi- cal rings, such as WDVV equation, the Mumford relations, the string and dilaton equations (g = 0;1;2) etc. and new formulas for …⁄(‚gk+1 + ¢¢¢ + ˆ g +k n+1).

Experiments on the simultaneous partitioning of divalent metal ions were carried out in the system K2Mg6Al2Si6O20(OH)4 (phlogopite) − KCl - (Ni2+,Mg2+,Co2+,Zn2+,Fe2+,Mn2+,Ca2+,Sr2+) Cl2 - H2O in the temperature range of 500 to 800 °C at 100 MPa, using the pressure vessel of a cold seal type. The partition coefficient KPN (Phl) for the ion exchange reaction between phlogopite (Phl) and aqueous chloride solution (aq) can be expressed as follows: KPN (Phl) = (X1/6K2Me6Al2Si6O20(OH)4 / X1/6K2Mg6Al2Si6O20(OH)4) Phl / (mMeCl20 / mMgCl20)aq where Me designates divalent metal ion, m: molality, and Xi: mole fraction of end-member i in biotite solid solution. The partition coefficient - ionic radius (PC-IR) curve marks a peak between Mg2+ and Fe2+. Zn2+ shows the same negative anomaly in the partition coefficients as observed in other minerals with 6-fold sites. Co2+ also represents such a negative anomaly as was previously found in tremolite and hedenbergite. Based on the previous and present experimental results, it is considered that the anomaly of Co2+ may be related with polymerization of Si tetrahedra.

A convergence process with a new type of localized orbital (LO) is proposed for self-consistent field (SCF) molecular orbital (MO) calculations on proteins. Recently, an all-electron density functional (DF) calculation on cytochrome c was achieved by a convergence method in which the initial electron density of a peptide was constructed by linking the electron density of small peptides. However, its convergence was slow and insufficient in SCF calculations for long peptides. In this paper a new kind of LO called the ‘quasi-canonical localized orbital (QCLO)’ is formulated and a computational process with QCLOs is proposed to improve the SCF convergence. The QCLO is localized in a certain region of a molecule, but it is also the canonical MO of the region. In test calculations on a seven-residue peptide, the error in the initial total energy calculated with QCLOs was about one twentieth of that by cut and paste of the electron density, and the number of SCF iterations was reduced markedly. Future applicati...

Systemic light-chain deposition due to plasma cell dyscrasias manifests as a form of restrictive cardiomyopathy with diastolic ventricular dysfunction. Although these manifestations are likely to be cardiac amyloidosis, whether these pathological conditions are reversible after treatment of the underlying plasma cell disorders is unknown. To our knowledge, we describe the first patient with cardiac light-chain deposition due to multiple myeloma in whom echocardiographic and biochemical factors of cardiac function were ameliorated dramatically after remission of this disorder. We emphasize that restrictive cardiomyopathy due to light-chain deposition may be reversible and have a relatively better prognosis after remission of plasma cell dyscrasias.

Despite its importance, carrier conduction in electrical insulators is poorly understood. This work presents a computational study of hole conduction in single crystalline alkanes (n-C18H38 and n-C36H74). Hole mobilities are computed with the combination of molecular dynamics simulation, quantum chemical calculation, and the kinetic Monte Carlo method. The hole hopping rate is computed by the Fermi golden rule rate kernel without high temperature approximation. A strong correlation between the anisotropy of hole mobility and crystalline morphology is found. Hole mobilities in the direction of the c axis are more than an order of magnitude larger than those in the a − b plane. At room temperature, hole mobility is increased by roughly a factor of 10 due to the thermal motion of molecules. Computed anisotropic hole mobilities are in reasonable agreement with experimental values when the effect of dynamic disorder is taken into account. The results strongly indicate that hole transfer in crystalline alkane occurs in the phonon-assisted transport regime.

To understand electronic properties and reactivities of proteins, we developed a molecular orbital (MO) program ProteinDF based on the density functional theory with Gaussian functions. By using it, we recently performed an all-electron calculation on a typical hemoprotein, cytochrome c. ProteinDF was coded by the object-oriented language C++ to construct the complex MO program for calculations on proteins with over a thousand orbitals. This program was parallelized for distributed parallel processing systems such as workstation clusters. In this Letter, we report parallelization methods by using the object-oriented technology in ProteinDF and their efficiency.

An all-electron wavefunction of horse heart d 6 -low-spin ferrocytochrome c (ferrocyt. c ) was calculated by our Gaussian-based density functional theory (DFT) molecular orbital (MO) program, ProteinDF with a workstation cluster. It may be the first full-scale DFT calculation of a metalloprotein, and the numbers of orbitals and auxiliary functions are 9600 and 17 578, respectively. We show that the highest occupied MO (HOMO) derives from 3d orbitals of heme Fe and is unexpectedly delocalized while preserving the essential atomic character, which will give room for consideration of the electron transfer processes between proteins. The potential of MO calculations on larger proteins is also discussed with the computational data of cytochrome c (cyt. c ).

An all-electron calculation of the antihypertensive and antiviral protein BDS-I from the sea anemone Anemonia sulcata was carried out using the density functional method based on Gaussian-type orbitals with workstations. Our computer program ProteinDF coded by the object-oriented language C++, was originally designed for all-electron calculations of proteins and controlled in parallel with high efficiency. The numbers of residues, atoms, orbitals and auxiliary functions of the calculated protein were 43, 629, 3615 and 6545, respectively. This Letter reports timing data of the computation and some calculated electronic properties. Our program will open the door for advanced studies of larger proteins.

The ionization potentials of one-electron oxidized states of cytochrome c 3 were evaluated by numerical calculations. In the ionization processes from cytochrome c 3 0+ to c 3 1+ , four ionization potentials were observed with respect to four hemes involved in cytochrome c 3 . Ab initio SCF MO calculations were carried out for the four heme complexes to obtain their ionization potentials under vacuum (IP vacuum s). The electrostatic potentials (EPs) which the apo-protein and the aqueous solvent produce at the heme irons were calculated by the particle–particle/particle–mesh (PPPM) algorithm based on the self-consistent boundary (SCB) method. Final theoretical ionization potentials of cytochrome c 3 (IP protein s) were evaluated as the sum of IP vacuum s and EPs. The calculated IP protein s successfully reproduced the order of corresponding experimental values. The maximum difference among IP protein s was 130 mV which was approximately twice as large as that of experimental ones. The small differences among IP protein s were given by the delicate cancellations of IP vacuum s and EPs. We also discuss the detailed electronic structures of hemes in cytochrome c 3 .

A restricted open shell Kohn–Sham (ROKS) equation is introduced in this article. This ROKS equation was constructed analogously to the restricted open shell Hartree–Fock (ROHF) equation. We derived a set of simultaneous eigenequations by the variation of orbitals and combined them into a unified ROKS equation. A program module to solve the ROKS equation was coded by the object-oriented language C++ to realize the software reliability and an efficient use of the limited memory. The module was implemented into a density functional theory (DFT) program we had developed. We solved a cationic state of bis(imidazole)porphinato-iron by our program with the ROKS method. The complex is a model for the reaction centers embedded in cytochrome c 3 . For the comparison of the electron distribution, the restricted Kohn–Sham (RKS) and the unrestricted Kohn–Sham (UKS) calculations were also carried out for the neutral state and the cationic state of the model complex, respectively.

To test the hypothesis that anti-atherogenicity in women exerts beneficial effects to prevent restenosis formation after coronary angioplasty, we studied 493 men (988 lesions) and 81 women (159 lesions), aged 40-60 years, who had undergone successful balloon angioplasty and had follow-up angiography, 4.9 +/- 4.1 months later. We compared the extent of restenosis between men and women, and between pre- and post-menopausal women, which was assessed by a categorical definition of restenosis (more than 50% diameter stenosis at follow-up) and by percent diameter measured immediately after angioplasty and at follow-up. Hypertension was more frequent in women and a significantly lower percentage of women smoked. In women, the levels of total cholesterol and low-density lipoprotein cholesterol were higher. The location of dilated lesions, frequency of angioplasty for lesions with chronic total occlusion, and frequency of emergency angioplasty in patients with unstable angina or acute myocardial infarction were similar in men and women. Restenosis formation, estimated by the categorical definition or percent diameter, did not differ between men and women, or between pre- and post-menopausal women. Menopausal status or sex was not an independent predictor of restenosis by multivariate analysis. Thus, the benefit of anti-atherogenicity in women does not play an important role in preventing restenosis after coronary angioplasty.

In this article, we propose a new molecular orbital program for all-electron calculation of proteins which is based on density functional theory. To carry it out in a fully analytical way, we adopted the (pure-) analytical Xα method and modified it for saving a lot of memories for large-scale calculations. The recent software technology sophisticated in information science is inevitably applied to achieve calculations of large molecular systems. The program is coded by the object-oriented language C + +, its output is shown graphically, and the most of the procedures in this program are controlled through an efficient graphical user interface developed by ourselves. Such technology supports the safe construction of the huge software, the tidy representation of enormous data, and the ready control of complex calculations. Test calculations with various sizes of glycine polypeptides indicate that the computation time is proportional to the 1.7 powers of the number of residues. This result suggests that the all-electron calculations of proteins consisting of over 1000 atoms could be performed with distributed and/or massively parallel computers. © 1997 John Wiley & Sons, Inc. Int J Quant Chem 63: 245–256, 1997

Oestrogen producing adrenocortical tumours are extremely rare. We report a 65-year-old woman who presented with abnormal vaginal bleeding, with no significant abnormalities in her uterus or ovaries, who was found to have a right adrenal mass by radiological examination. Excessive secretion of oestrogens from the tumour was demonstrated by adrenal venous sampling. Basal levels of corticosteroids were within normal limits. Adrenalectomy was performed and pathological examination revealed an adrenocortical adenoma measuring 5.5 cm in its greatest dimension, in which both clear and compact tumour cells were observed. Oestrogen levels normalized following the removal of the adrenal mass. Tissue concentrations of oestrone and oestradiol in the tumour were 6.9 (69.5 pmol/g wet tissue weight) and 34.6 (93.6 pmol/g wet tissue weight)-fold greater respectively than those of adjacent non-neoplastic adrenal cortex. Aromatase activity in the tumour tissue determined by the 3H-water method was 118.6 pmol/h/mg protein, equivalent to that of a full-term human placenta. Immunohistochemical analysis of aromatase demonstrated immunoreactivity in the tumour cells, especially in compact cells, but not in adjacent non-neoplastic adrenal cells. This is the first reported case of an oestrogen producing adrenocortical adenoma in which aromatase in the tumour cells was documented.