Enhancing the accuracy of virtual screening: molecular dynamics with quantum-refined force fields

Summary A methodology aimed at improving the accuracy of current docking–scoring procedures is proposed, and validated through detailed tests of its performance in predicting the activity of HIV-1 protease inhibitors. This methodology is based on molecular dynamics simulations using a force field whose effective charges are refined by means of a novel procedure that relies on quantum-mechanical calculations and preserves the internal consistency of the parameterization scheme.     

Nuclear magnetic resonance in inhomogeneous magnetic fields

The response of the spin system has been investigated by numerical simulations in the case of a nuclear magnetic resonance (NMR) experiment performed in inhomogeneous static and radiofrequency fields. The particular case of the NMR-MOUSE was considered. The static field and the component of the radiofrequency field perpendicular to the static field were evaluated as well as the spatial distribution of the maximum NMR signal detected by the surface coil. The NMR response to various pulse sequences was evaluated numerically for the case of an ensemble of isolated spins (1/2). The behavior of the echo train in Carr-Purcell-like pulse sequences used for measurements of transverse relaxation and self-diffusion was simulated and compared with the experiment. The echo train is shown to behave qualitatively differently depending on the particular phase schemes used in these pulse sequences. Different echo trains are obtained, because of the different superposition of Hahn and stimulated echoes forming mixed echoes as a result of the spatial distribution of pulse flip angles. The superposition of Hahn and stimulated echoes originating from different spatial regions leads to distortions of the mixed echoes in intensity, shape, and phase. The volume selection produced by Carr-Purcell-like pulse sequences is also investigated for the NMR-MOUSE. The developed numerical simulation procedure is useful for understanding a variety of experiments performed with the NMR-MOUSE and for improving its performance. Copyright 2000 Academic Press.     

Some basic principles in dynamic theory of viscoelastic materials with voids

According to the basic idea of classical yin-yang complementarity and modern dual-complementarity, in a simple and unified way proposed by Luo, some basic principles in the dynamic theory of viscoelastic materials with voids can be estab- lished systematically. In this paper, an important integral relation in terms of con- volutions is given, which can be considered as the generalized principle of virtual work in mechanics. Based on this relation, it is possible not only to obtain the principle of virtual work and the reciprocal theorem, but also to derive systemati- cally the complementary functionals for the eight-field, six-field, four-field simpli- fied Gurtin-type variational principles and the potential energy-functional for the two-field one in the dynamic theory of viscoelastic materials with voids by the generalized Legendre transformations given in this paper. Furthermore, with this approach, the intrinsic relationship among various principles can be explained clearly.     

球差对调焦函数的影响

红外导引头成像光斑测试仪系统的球差对成像光斑质量有很大的影响,降低了光斑的能量集中度.通过对球差因素影响的研究,构造的调焦评价函数能更精确地分辨最佳像面,从而通过自动聚焦寻找最佳像面位置,是测试仪评价其光学系统质量的一个重要环节.     

基于虚拟仪器的视频图像采集系统设计

应用虚拟仪器技术，在Lab VIEW7．1开发平台上设计了利用IMAQ Vision for LabVIEW基于NI IMAQ 1405图像采集卡的图像采集系统。该系统对CCD电视、红外热像仪等输出的模拟视频图像具有采集能力，且结构简单，扩展方便，效率高，通用性强，显示了虚拟仪器技术的在信息技术研发中的显著优势。     

低速气流三参数动态测量软件初探

本文采用虚拟仪器概念和技术,构建了三孔探针动态测量系统。该系统集成了高速数据采集、储存及现代数据处理模块,通过该系统可动态显示低马赫数下压气机内部流场的总压、静压、速度矢量等物理参数的变化趋势,并可对动态信号进行时域显示和频域分析。系统还具备自动标定、零漂消除及线性度拟合的功能,实现了流场动态测试技术在线处理与测试同步进行的目的。     

An illustrated theory of hyperbolic virtual polytopes

The paper gives an illustrated introduction to the theory of hyperbolic virtual polytopes and related counterexamples to A.D. Alexandrov’s conjecture.      

Unconventional Hamilton-type variational principles for electromagnetic elastodynamics

According to the basic idea of classical yin-yang complementarity and modern dual-complementarity, in a simple and unified new way proposed by Luo, the unconventional Hamilton-type variational principles for electromagnetic elastodynamics can be established systematically. This new variational principles can fully characterize the initial-boundary-value problem of this dynamics. In this paper, the expression of the generalized principle of virtual work for electromagnetic dynamics is given. Based on this equation, it is possible not only to obtain the principle of virtual work in electromagnetic dynamics, but also to derive systematically the complementary functionals for eleven-field, nine-field and six-field unconventional Hamilton-type variational principles for electromagnetic elastodynamics, and the potential energy functionals for four-field and three-field ones by the generalized Legendre transformation given in this paper. Furthermore, with this approach, the intrinsic relationship among various principles can be explained clearly.     

Pharmacophore Modeling and Virtual Screening of Novel Inhibitors for c-Kit Kinase

The stem cell factor receptor (c‐Kit) has been known to play critical roles in regulating numerous aspects of cellular behavior including cell growth, differentiation, migration and metabolism. In this investigation, a three‐dimensional pharmacophore model of c‐Kit inhibitors has been established by using the HypoGen algorithms implemented in the catalyst software package. The best quantitative pharmacophore model, hypothesis 1, which has the highest correlation coefficient (0.989), consists of one hydrogen bond acceptor, two hydrogen bond donors and one hydrophobic feature. To our knowledge, this is the first report on the pharmacophore modeling study of c‐Kit inhibitors. The best hypothesis, hypothesis 1, was used to screen molecular structural databases, including Specs and China Natural Products Database for potential lead compounds. The hit compounds were subsequently subjected to filtering by Lipinski's rules and docking study to refine the retrieved hits and as a result to reduce the rate of false positive. Finally 28 compounds were purchased or synthesized for further in vitro assay against several human tumour cell lines including A549, MCF‐7, HepG2 and PC‐3, in which c‐Kit is overexpressed. Two compounds show very low micromolar inhibition potency against the PC‐3 and HepG2 cell lines respectively. And they were selected for further modification and testing.