Computational Design of Novel Allosteric Inhibitors for Plasmodium falciparum DegP

The serine protease, DegP exhibits proteolytic and chaperone activities, essential for cellular protein quality control and normal cell development in eukaryotes. The P. falciparum DegP is essential for the parasite survival and required to combat the oscillating thermal stress conditions during the infection, protein quality checks and protein homeostasis in the extra-cytoplasmic compartments, thereby establishing it as a potential target for drug development against malaria. Previous studies have shown that diisopropyl fluorophosphate (DFP) and the peptide SPMFKGV inhibit E. coli DegP protease activity. To identify novel potential inhibitors specific to PfDegP allosteric and the catalytic binding sites, we performed a high throughput in silico screening using Malaria Box, Pathogen Box, Maybridge library, ChEMBL library and the library of FDA approved compounds. The screening helped identify five best binders that showed high affinity to PfDegP allosteric (T0873, T2823, T2801, {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, CD00811) and the catalytic binding site (T0078L, T1524, T2328, BTB11534 and 552691). Further, molecular dynamics simulation analysis revealed {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, BTB11534 as the best hits forming a stable complex. WaterMap and electrostatic complementarity were used to evaluate the novel bio-isosteric chemotypes of {"type":"entrez-protein","attrs":{"text":"RJC02337","term_id":"1480409465","term_text":"RJC02337"}}RJC02337, that led to the identification of 231 chemotypes that exhibited better binding affinity. Further analysis of the top 5 chemotypes, based on better binding affinity, revealed that the addition of electron donors like nitrogen and sulphur to the side chains of butanoate group are more favoured than the backbone of butanoate group. In a nutshell, the present study helps identify novel, potent and Plasmodium specific inhibitors, using high throughput in silico screening and bio-isosteric replacement, which may be experimentally validated.     

双层桥梁耦合系统的强迫振动

本文研究作为双层桥模型的梁方程耦合系统，利用Ｌｅｒａｙ－Ｓｃｈａｕｄｅｒ不动点定理，得到了一个关于这种系统的解的存在性定理，它类似于ＭｃＫｅｎｎａ和Ｗａｌｔｅｒ文２中关于吊桥方程的一个定理。     

共振下n维Lienard型方程的2π周期解

本文在跨共振点条件下证明n维Lienard型方程存在2π周期解.     

具有开发的非自治单种群生态系统研究

研究了具有开发的单种群非自治周期系统．利用非自治微分方程理论．以及变分法理论和泛函极值的Euler方程方法,得到了该开发系统的持续生存性．周期解存在性，全局渐近稳定性．研究了在开发情况下的最大收获量问题，以及取得最大经济效益下的收获问题等．     

具P-Laplacian算子型周期边值问题解的存在性

本文利用拓扑度理论和一些分析技巧讨论了具p—Laplacian算子型周期边值问题(φp(χ’))’+d/dt gradF(χ)+gradG(χ)=e(t),χ(0)=χ(T),χ’(0)=χ’(T)解的存在性,在对阻尼项d/dtgradF(χ)没有任何限制的前提下,给出了解存在的充分条件.     

On the counting function of the lattice profile of periodic sequences

The lattice profile analyzes the intrinsic structure of pseudorandom number sequences with applications in Monte Carlo methods and cryptology. In this paper, using the discrete Fourier transform for periodic sequences and the relation between the lattice profile and the linear complexity, we give general formulas for the expected value, variance, and counting function of the lattice profile of periodic sequences with fixed period. Moreover, we determine in a more explicit form the expected value, variance, and counting function of the lattice profile of periodic sequences for special values of the period.     

多维Lotka-Uolterra周期系统周期解的存在性及其全局吸引性

研究了m-维离散Lotka-Volterra竞争系统，并获得了该系统周期解的存在性及其全局吸引性.     

具有避难所的非自治竞争系统的持续生存和全局稳定性

考虑一个四缀块模型，其中一缀块里有三个竞争种群，另外三个分别是它们的避难所，并且种群能在竞争缀块和各自的避难所间相互扩散．在一定的条件下，我们给出了此模型的持续生存，周期性和全局稳定性．     

Periodic solutions of second-order differential inclusions systems with p-Laplacian

Some existence results are obtained for periodic solutions of nonautonomous second-order differential inclusions systems with p-Laplacian.     

Duffing方程的唯三周期解问题

考虑Duffing方程x+g(x,t)=h(t),在g(x,t)满足简单的凸凹性条件。以及g＇(x,t)跨越第一共振点时,本文指出,当强迫振动项h(t)充分小时,所讨论的Duffing方程的2π周期解恰有三个.