Receptor-independent 4D-QSAR analysis of a set of norstatine derived inhibitors of HIV-1 protease

A training set of 27 norstatine derived inhibitors of HIV-1 protease, based on the 3(S)-amino-2(S)-hydroxyl-4-phenylbutanoic acid core (AHPBA), for which the -log IC(50) values were measured, was used to construct 4D-QSAR models. Five unique RI-4D-QSAR models, from two different alignments, were identified (q(2) = 0.86-0.95). These five models were used to map the atom type morphology of the lining of the inhibitor binding site at the HIV protease receptor site as well as predict the inhibition potencies of seven test set compounds for model validation. The five models, overall, predict the -log IC(50) activity values for the test set compounds in a manner consistent with their q(2) values. The models also correctly identify the hydrophobic nature of the HIV protease receptor site, and inferences are made as to further structural modifications to improve the potency of the AHPBA inhibitors of HIV protease. The finding of five unique, and nearly statistically equivalent, RI-4D-QSAR models for the training set demonstrates that there can be more than one way to fit structure-activity data even within a given QSAR methodology. This set of unique, equally good individual models is referred to as the manifold model.     

Cumulant functions in optical coherence theory

Cumulant functions are introduced to describe the statistical state of a radiation field. These functions are simply related to the optical coherence functions but have some interesting features. It is shown that if the cumulant functions of all orders greater than some numberN ₀ vanish then they also vanish for all orders greater than 2. Thermal field is the only field having this property. This property holds whether the field is described by a classical stochastic process or by a quantum density operator. Further the particular operator ordering used in defining these cumulant functions for the quantized field affects only the second order cumulant function. To describe the statistical state of a vector field such as partially polarized or unpolarized radiation, one would need to introduce cumulant tensors.     

A simple clustering technique to improve QSAR model selection and predictivity: application to a receptor independent 4D-QSAR analysis of cyclic urea derived inhibitors of HIV-1 protease

A training set of 50 tetrahydropyrimidine-2-one based inhibitors of HIV-1 protease, for which the -log K(i) values were measured, was used to construct receptor independent 4D-QSAR models. A novel clustering technique was employed to facilitate and improve model selection as well as test set predictions. Following the manifold model theory, five unique models were chosen by the clustering algorithm (q(2) = 0.81-0.84). The models were used to map the atom type morphology of the inhibitor binding site of HIV-1 protease as well as to predict the potencies (-log K(i)) of 10 test set compounds. The rank-difference correlation coefficient was used to evaluate the quality of the test set predictions, which was improved from 0.39 to 0.68 when the clustering technique was applied. The set of five models, collectively, identify the important binding characteristics of the HIV protease receptor site. This study demonstrates that the selected simple clustering technique provides a discrete algorithm for model selection, as well as improving the quality of test set, or unknown, compound prediction as determined by the rank-difference correlation coefficient.     

Gas phase activation energy for unimolecular dissociation of biomolecular ions determined by focused RAdiation for gaseous multiphoton ENergy transfer (FRAGMENT)

We present a novel approach for the determination of activation energy for the unimolecular dissociation of a large (>50 atoms) ion, based on measurement of the unimolecular dissociation rate constant as a function of continuous-wave CO(2) laser intensity. Following a short ( approximately 1 s) induction period, CO(2) laser irradiation produces an essentially blackbody internal energy distribution, whose 'temperature' varies inversely with laser intensity. The only currently available method for measuring such activation energies is blackbody infrared radiative dissociation (BIRD). Compared with BIRD, FRAGMENT: (a) eliminates the need to heat the surrounding ion trap and vacuum chamber to each of several temperatures (each requiring hours for temperature equilibration); (b) offers a three-fold wider range of effective blackbody temperature; and (c) extends the range of applications to include initially cold ions (e.g., gas-phase H/D exchange). Our FRAGMENT-determined activation energy for dissociation of protonated bradykinin, 1.2 +/- 0.1 eV, agrees within experimental error to the value, 1.3 +/- 0.1 eV, previously reported by Williams et al. from BIRD experiments. Copyright 1999 John Wiley & Sons, Ltd.     

Additive NMR chemical shift parameters for deshielded methine protons

The use of additive parameters for the prediction of NMR chemical shifts is widely practised. However, no correlations are available for highly deshielded methine protons. In this work, methine chemical shifts have been studied using both multiple linear regression analysis and Simplex function minimization in an effort to determine under what limiting circumstances the additivity of shift parameters can be expected to apply. As expected, it was not possible to explain satisfactorily all methine shifts with a single set of substituent parameters. However, if only the deshielded cases were considered (H—CXYZ, where at least two of the three groups X, Y, and Z are electron-withdrawing), a much better set of parameters could be determined. Using a data set of 440 of these deshielded methine shifts, involving 31 different substituents, a standard error of estimate of 0.20 ppm is found for protons spread between 3.0 and 7.5 ppm.     

铌酸锶钡薄膜的微结构与电光性能的研究

本文叙述了使用溶胶凝胶法在MgO(0 0 1)的衬底上制备铌酸锶钡薄膜的过程 ,膜层厚度可达 5 μm。通过X射线衍射、摇摆曲线、扫描、拉曼散射光谱等方法研究了薄膜的微结构性能 ,实验发现 ,铌酸锶钡薄膜具有了较好的 (0 0 1)方向的优先取向性能 ,并且随着薄膜厚度的增加 ,其晶体取向性也会随之不断改进。熔石英的透明衬底上生长的SBN薄膜具有较大的电致双折射效应 ,其有效电光系数能够高达 6 6 2× 10 -11m/V。