MOLECULAR DYNAMICS STUDIES OF BONDORIENTATIONAL ORDER IN MOLTEN AND QUENCHED-VITREOUS STATE OF LiCI

In this paper, we give further discussions about our new method of bond spherical har-monics with equal number of near neighborst, and study the molten salt LiCl and itsquenching process by means of molecular dynamics simulation. The bond order parametersQ_l at different temperatures are calculated by averaging the Q_l values of the computer-generated instantaneous configurations at each time-step. By consulting the Q_l histogramsof the linear combination models with a parameter of square deviation σ we find that theQ_l Listograms from the simulation and those from the combination model with 90% localtetrahedron structure are very similar. The results indicate that the local bond orientationin the quenched LiCl system tends strongly to be tetrahedron. The local bond-orientationalorders in the quenching process can be described by the same linear combination, but thesquare deviation varies with the temperature. The square deviation decreases with thelowering of temperature and drops rapidly when the glass transition takes place. The bondangle distributions are also calculated and it is found that the angles gather about 109°(the=bond angle of tetrahedron) and the peaks of the distributions Lave a wider spread as temper-iature increases, in accordance with the results from Q_l.

AN EFFICIENT APPROACH FOR THE IDENTIFICATION OF CARBON SKELETON AND FUNCTIONAL GROUP IN CHEMICAL STRUCTURE

Ⅰ. INTRODUCTIONSince the DENDRAL system was elaborated by Standford University at the beginning of 1960s, structure elucidation systems have aroused a lot of researchers’ interest. On the basis of our multi-spectroscopic searching system, we have successfully built up a multi-

Molecular dynamics simulation of calcium fluoride——Crystalline, superionic, molten and quenched-amorphous phases

The results from the molecular dynamics simulations on crystalline, superionic, molten and quenched-amorphous states of calcium fluoride system are reported. The Ca++ and F- sublattices are studied by using the method of bond order parameters. The result shows that both Ca++ and F- sublattices can be described with the bond-orientation normal distribution model. In the superionic phase the Ca++ cations keep their original stable fcc frame, but in the F- case random distortion generates from their original simple cubic (sc) structure. The simulation on the molten phase gives three radial distribution functions that are difficult to separate from the experimental X-ray diffraction data. The simulation of quenched-amorphous state shows that a dense random packing of equivalent spheres centered by Ca++ cations occurs in the system simulated. However, the system quenched is not stable enough because the Ca++ cation and F- anions around it do not form themselves into a certain configuration.

APPLICATION OF A C-13 NMR TOPOLOGICAL MODEL TO THE STRUCTURE ELUCIDATION OF ORGANIC COMPOUNDS

This paper presents an approach which can elucidate automatically the structures of simple organic compounds from their C-13 NMR spectral data by using a computer. Based on a substructure/C-13 NMR chemical shift topological correlation model, the approach deduces the candidate substructures and the constraints for the substructure assembling from the molecular formula and C-13 NMR spectral data. Then, candidate structures are generated under these constraints by assembling the candidate substructures in a partial superposition manner. Candidate substructures or structures are evaluated once they are generated in order to eliminate those conflicting with the original data as early as possible. The evaluation of a (sub)structure is mainly carried out by simulating its C-13 NMR (sub) spectrum, which is again based on the model, and comparing the simulated spectrum with the original data.

Exhaustive generation of specific structures contained in generic structure

Since Kekule, chemists have regarded molecular structural diagratim as one of the most important means to describe compounds. With many years’ effort, the structure handling approaches based on the chromatic graph theory have been successfully applied to structure representation, specific structure canonicalisation, structure and substructure searching and structure registry. The specific structure handling systems at the level of database management system have been built up. However, the problem of generic structure handling, due to its inherent complexity, has not been completely resolved yet.

Discovery of Anti-SARS Coronavirus Drug Based on Molecular Docking and Database Screening

The active site of 3CL proteinase (3CLpro) for coronavirus was identified by comparing the crystal structures of human and porcine coronavirus. The inhibitor of the main protein of rhinovirus (Ag7088) could bind with 3CLpro of human coronavirus, then it was selected as the reference for molecular docking and database screening. The ligands from two databases were used to search potential lead structures with molecular docking. Several structures from natural products and ACD-SC databases were found to have lower binding free energy with 3CLpro than that of Ag7088. These structures have similar hydrophobicity to Ag7088. They have complementary electrostatic potential and hydrogen bond acceptor and donor with 3CLpro, showing that the strategy of anti-SARS drug design based on molecular docking and database screening is feasible.

From pharmacophore to leads: Bioactive compound discovery via computer-aided techniques

Based on the concept of Green Chemistry, a new procedure of finding bioactive compounds and their synthetic routes by computer-aided techniques was proposed. The procedure consists of pharmacopoeia search against a 3D structural database of natural products for lead discovery and computer-aided synthesis design for avoiding un useful synthetic experiments. This work demonstrated that computer aided drug design and synthesis design would help us to make the consideration of environmental concerns systematically, rather than having to deal later with the unnecessary waste chemicals. Thus, it is shown that chemical computer-aided design (CAD) is an indispensable part of Green Chemistry.

3D-QSAR Study on Diindolylmethane and Its Analogues with Comparative Molecular Field Analysis (CoMFA)

Comparative molecular field analysis (CoMFA), a three dimensional quantitative structure-activity relationship (3D-QSAR) method was applied to a series of diindolylmethane (DIM) analogs to study the relationship between their structure and their induction of CYP 1A1-associated ethoxyresorufin-O-deethylase (EROD) activity. A DISCO model of pharmacophore was derived to guide the superposition of the compounds. The coefficient of cross-validation (q 2) and non cross-validation (r 2) for the model established by the study are 0.827 and 0.988 respectively, the value of variance ratio (F) is 103.53 and standard error estimate (SEE) is 0.044. These values indicate that the CoMFA model derived is significant and might have a good prediction for the catalytic activity of DIM compounds. As a consequence, the predicted activity values of new designed compounds were all higher than that of the reported value.

3D-QSAR Study on Apicidin Inhibit Histone Deacetylase

For Histone Deacetylase (HDAC) Inhibitor, four 3D-QSAR models for four types of different activities,were constructed. The cross-validated q 2 value of CoMFA Model 1 is 0.624 and the noncross-validated r 2 value is 0.939. The cross-validated q 2 value of Model 2 for training set is 0.652 and the noncross-validated r 2 value is 0.963. The cross-validated q 2 value for Model 3 is 0.713,with noncross-validated r 2 value 0.947. The cross-validated q 2 value for Model 4 is 0.566 with noncross-validated r 2 value 0.959. Their predicted abilities were validated by different test sets which did not include in training set. Then the relationship between substituents and activities was analyzed by using these models and the main influence elements in different positions (positions 8 and 14) were found. The polar donor electron group of position 8 could increase the activity of inhibition of HDAC,because it could form chelation with the catalytic Zn. Suitable bulk and positive groups at position 14 are favorable to anti-HDAC activity. These models could well interpret the relationship between inhibition activity and apicidin structure affording us important information for structure-based drug design.