Insights into the Allosteric Effect of SENP1 Q597A Mutation on the Hydrolytic Reaction of SUMO1 via an Integrated Computational Study

Small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a cysteine protease that catalyzes the cleavage of the C-terminus of SUMO1 for the processing of SUMO precursors and deSUMOylation of target proteins. SENP1 is considered to be a promising target for the treatment of hepatocellular carcinoma (HCC) and prostate cancer. SENP1 Gln597 is located at the unstructured loop connecting the helices α4 to α5. The Q597A mutation of SENP1 allosterically disrupts the hydrolytic reaction of SUMO1 through an unknown mechanism. Here, extensive multiple replicates of microsecond molecular dynamics (MD) simulations, coupled with principal component analysis, dynamic cross-correlation analysis, community network analysis, and binding free energy calculations, were performed to elucidate the detailed mechanism. Our MD simulations showed that the Q597A mutation induced marked dynamic conformational changes in SENP1, especially in the unstructured loop connecting the helices α4 to α5 which the mutation site occupies. Moreover, the Q597A mutation caused conformational changes to catalytic Cys603 and His533 at the active site, which might impair the catalytic activity of SENP1 in processing SUMO1. Moreover, binding free energy calculations revealed that the Q597A mutation had a minor effect on the binding affinity of SUMO1 to SENP1. Together, these results may broaden our understanding of the allosteric modulation of the SENP1−SUMO1 complex.     

Electronic structure of strongly correlated systems: recent developments in multiconfiguration pair-density functional theory and multiconfiguration nonclassical-energy functional theory

Strong electron correlation plays an important role in transition-metal and heavy-metal chemistry, magnetic molecules, bond breaking, biradicals, excited states, and many functional materials, but it provides a significant challenge for modern electronic structure theory. The treatment of strongly correlated systems usually requires a multireference method to adequately describe spin densities and near-degeneracy correlation. However, quantitative computation of dynamic correlation with multireference wave functions is often difficult or impractical. Multiconfiguration pair-density functional theory (MC-PDFT) provides a way to blend multiconfiguration wave function theory and density functional theory to quantitatively treat both near-degeneracy correlation and dynamic correlation in strongly correlated systems; it is more affordable than multireference perturbation theory, multireference configuration interaction, or multireference coupled cluster theory and more accurate for many properties than Kohn–Sham density functional theory. This perspective article provides a brief introduction to strongly correlated systems and previously reviewed progress on MC-PDFT followed by a discussion of several recent developments and applications of MC-PDFT and related methods, including localized-active-space MC-PDFT, generalized active-space MC-PDFT, density-matrix-renormalization-group MC-PDFT, hybrid MC-PDFT, multistate MC-PDFT, spin–orbit coupling, analytic gradients, and dipole moments. We also review the more recently introduced multiconfiguration nonclassical-energy functional theory (MC-NEFT), which is like MC-PDFT but allows for other ingredients in the nonclassical-energy functional. We discuss two new kinds of MC-NEFT methods, namely multiconfiguration density coherence functional theory and machine-learned functionals.

This feature article overviews recent work on active spaces, matrix product reference states, treatment of quasidegeneracy, hybrid theory, density-coherence functionals, machine-learned functionals, spin–orbit coupling, gradients, and dipole moments.     

Interfacial Charge Transfer Induced Electronic Property Tuning of MoS_2 by Molecular Functionalization

The modulation of electrical properties of MoS_2 has attracted extensive research interest because of its potential applications in electronic and optoelectronic devices.Herein,interfacial charge transfer induced electronic property tuning of MoS_2 are investigated by in situ ultraviolet photoelectron spectroscopy and x-ray photoelectron spectroscopy measurements.A downward band-bending of MoS_2-related electronic states along with the decreasing work function,which are induced by the electron transfer from Cs overlayers to MoS_2,is observed after the functionalization of MoS_2 with Cs,leading to n-type doping.Meanwhile,when MoS_2 is modified with 2,3,5,6-tetrafluoro-7,7,8,8-tetracyanoquinodimethane(F_4-TCNQ),an upward band-bending of MoS_2-related electronic states along with the increasing work function is observed at the interfaces.This is attributed to the electron depletion within MoS_2 due to the strong electron withdrawing property of F_4-TCNQ,indicating p-type doping of MoS_2.Our findings reveal that surface transfer doping is an effective approach for electronic property tuning of MoS_2 and paves the way to optimize its performance in electronic and optoelectronic devices.     

Possible light neutral boson and particle mass quantization

Qualities of nucleons, such as the fundamental parameter mass, might be modified in extreme conditions relative to those of isolated nucleons. We show the ratio of the EMC-effect tagged nucleon mass to that of the free one(m*/m);these values are derived from the nuclear structure function ratio between heavy nuclei and deuterium measured in the electron Deep Inelastic Scattering(DIS) reaction in 0.3≤x≤0.7. The increase in m*/mwith A-1/3 is phenomenologically interpreted via the release of a color-singlet cluster formed by sea quarks and gluons in bound nucleons holding high momentum in the nucleus, from which the mass and fraction of non-nucleonic components in nuclei can be deduced. The mass of color-singlet clusters released per short range correlated(SRC) proton in the high momentum region(k > 2 fm-1) is extracted to be 16.890 ±0.016 MeV/c2, which evidences the possibility of a light neutral boson and quantized mass of matter.     

Anisotropic Superconducting Properties of Kagome Metal CsV_3Sb_5

We systematically measure the superconducting(SC) and mixed state properties of high-quality CsV_3 Sb_5 single crystals with T_c～3.5 K.We find that the upper critical field H_(c2)(T) exhibits a large anisotropic ratio of H_(c2)~(ab)/H_(c2)~c～9 at zero temperature and fitting its temperature dependence requires a minimum two-band effective model.Moreover,the ratio of the lower critical field,H_(c1)~(ab)/H_(c1)~c,is also found to be larger than 1,which indicates that the in-plane energy dispersion is strongly renormalized near Fermi energy.Both H_(c1)(T) and SC diamagnetic signal are found to change little initially below T_c～3.5 K and then to increase abruptly upon cooling to a characteristic temperature of ～2.8 K.Furthermore,we identify a two-fold anisotropy of in-plane angular-dependent magnetoresistance in the mixed state.Interestingly,we find that,below the same characteristic T～2.8 K,the orientation of this two-fold anisotropy displays a peculiar twist by an angle of 60° characteristic of the Kagome geometry.Our results suggest an intriguing superconducting state emerging in the complex environment of Kagome lattice,which,at least,is partially driven by electron-electron correlation.     

Common (π,π) Band Folding and Surface Reconstruction in Fe As-Based Superconductors

High resolution angle-resolved photoemission spectroscopy(ARPES) measurements are carried out on CaKFe_4 As_4,KCa_2 Fe_4 As_4 F_2 and(Ba_(0.6)K_(0.4))Fe_2 As_2 superconductors.Clear evidence of band folding between the Brillouin zone center and corners with a(π,π) wave vector has been found from the measured Fermi surface and band structures in all the three kinds of superconductors.A dominant ~(1/2)×~(1/2) surface reconstruction is observed on the cleaved surface of CaKFe_4As_4 by scanning tunneling microscopy(STM) measurements.We propose that the commonly observed ~(1/2)×~(1/2) reconstruction in the FeAs-based superconductors provides a general scenario to understand the origin of the(π,π) band folding.Our observations provide new insights in understanding the electronic structure and superconductivity mechanism in iron-based superconductors.     

正丁基正辛基亚砜萃取Au(Ⅲ)的NMR波谱研究

以亚砜的模型化合物正丁基正辛基亚砜液-液萃取Au(Ⅲ),对萃取剂及萃取配合物的1H NMR、13C NMR波谱特征进行讨论,研究了萃取时萃合物的结构及其动态变化.作者认为有机相中存在Au(Ⅲ)在正丁基正辛基亚砜(BOSO)与配合物之间快速交换的过程,该过程有利于Au(Ⅲ)从水相向有机相转移,也是形成NMR波谱特征的主要原因.核磁共振实验也说明了在两种酸度下Au(Ⅲ)均与亚砜基团中的氧原子配位,但萃取机理有所不同,核磁共振波潜的分析给出了萃取机理的直接证据.     

阵列微流控浓度梯度网络用于细胞-化学刺激反应研究

设计和制作了具有5组平行浓度梯度形成网络和30个细胞培养池的微流控芯片,该芯片集成了细胞接种、培养、梯度浓度化学刺激、标记和检测等功能单元。芯片为玻璃-PDMS杂合结构,微流控通道刻蚀于玻璃层。芯片细胞培养池设计了系列围堰结构以利于细胞贴壁。细胞接种、灌流培养和试剂引入通过外接微量注射泵控制完成。该芯片可以生成连续、稳定的平行浓度梯度。观察发现,围堰结构有利于细胞接种和生长,乳腺癌MCF-7细胞在芯片灌流培养条件下生长良好。利用该芯片检测了在接受As2O3和乙酰丝氨酸(NAC)梯度浓度刺激后乳腺癌MCF-7细胞内谷胱甘肽(GSH)水平以及细胞阿霉素敏感性的变化,分析乳腺癌细胞阿霉素敏感性与细胞内GSH水平的关系。MCF-7细胞内GSH水平的变化与刺激药物浓度呈剂量-效应依赖关系,在接受As2O3刺激后GSH水平有所下降;而在接受NAC刺激后GSH水平有所升高。MCF-7细胞阿霉素敏感性与GSH水平相关。在降低GSH水平后药物敏感性升高;而升高细胞内GSH水平后敏感性降低。这种阵列微流控浓度梯度网络可以用于高通量细胞-化学刺激反应研究,有潜力成为细胞水平大规模药物筛选的技术平台。     

超声喷雾电离源的研制与表征

研制了超声喷雾电离源(SSI)。采用核糖核酸A、溶菌酶等样品和商品化的线性离子阱质谱仪对该电离源进行了表征。实验发现,对于生物大分子,超声喷雾电离质谱(SSI-MS)能够获得与电喷雾质谱(ESI-MS)类似的多电荷离子。但与同等条件下ESI-MS所获得的谱图相比,SSI主要获得低价态的多电荷离子。在此基础上,系统考察了SSI-MS各主要操作参数对不同价态蛋白质多电荷离子信号强度的影响,并提出了SSI离子化的可能机理。结果表明,在喷雾气压3.4~3.6 MPa、喷雾口到质谱入口的距离4~6 mm、离子传输管温度250~300℃、样液流速50~100μL/min、2%~5%甲酸酸性且不含甲醇的条件下,各价态蛋白质离子信号强度及信号分布均达到最优;而离子传输管温度越高,喷雾压力越大或溶剂中甲醇等挥发性成分越高,则越有利于低价态离子的形成。     

光谱法研究吲哚美辛,舒林酸及其金属配合物与牛血清蛋白的相互作用

以曙红Y(Eosin Y)为探针,采用竞争结合法考查了非甾体抗炎药吲哚美辛和舒林酸及其相关的金属配合物与BSA的结合。在中性环境中,曙红Y的吸收光谱随着BSA的加入发生明显变化,结果表明,曙红Y与BSA之间的结合以静电作用为主,两者之间可能发生电子转移。曙红Y与BSA结合后,抗炎药吲哚美辛,舒林酸的加入可以破坏这种结合,曙红Y部分游离出来,其吸收值恢复,说明药物可以同样的方式结合到BSA上,抢占曙红Y在BSA上的结合位点。将药物转化为金属配合物后,与血清蛋白的亲和程度更强,铜(Ⅱ)的配合物最为突出,推测将非甾体抗炎药转化为铜配合物后,有更好的药理活性。