Novel Inhibitors of 2′-O-Methyltransferase of the SARS-CoV-2 Coronavirus

The COVID-19 pandemic is still affecting many people worldwide and causing a heavy burden to global health. To eliminate the disease, SARS-CoV-2, the virus responsible for the pandemic, can be targeted in several ways. One of them is to inhibit the 2′-O-methyltransferase (nsp16) enzyme that is crucial for effective translation of viral RNA and virus replication. For methylation of substrates, nsp16 utilizes S-adenosyl methionine (SAM). Binding of a small molecule in the protein site where SAM binds can disrupt the synthesis of viral proteins and, as a result, the replication of the virus. Here, we performed high-throughput docking into the SAM-binding site of nsp16 for almost 40 thousand structures, prepared for compounds from three libraries: Enamine Coronavirus Library, Enamine Nucleoside Mimetics Library, and Chemdiv Nucleoside Analogue Library. For the top scoring ligands, semi-empirical quantum-chemical calculations were performed, to better estimate protein–ligand binding enthalpy. Relying upon the calculated binding energies and predicted docking poses, we selected 21 compounds for experimental testing.     

高反射膜激光零几率损伤阈值的实验研究

在确定光学薄膜激光损伤阈值的实验数据处理过程中,发现一些样品的数据点分布偏离直线型式。对此,用国际标准规定的零几率来确定损伤阈值的同时,对测试数据点采用了不同的非直线拟合,也得到一个零几率损伤阈值。比较两者差异,并与实验测试结果对照,发现这些样品采用非直线拟合得出的零几率损伤阈值与实际情况更接近一些。     

Improved excitation uniformity in multiple‐quantum NMR experiments of mixtures

Multiple‐quantum ¹H NMR spectroscopy has been finding a renewed interest for its possible applications in the analysis of mixtures of small molecules, due to its simplification properties. A crucial aspect of this application of multiple‐quantum NMR is the sensitivity of the spectrum intensity to the molecular structure and to the parameterization of the experiment, which could result in the missing of some components. We demonstrate that a general scheme to overcome this drawback consists in varying the experiment parameterizations over a small number of values, selected according the values of the couplings and the relaxation rates. Copyright © 2013 John Wiley & Sons, Ltd.     

On the formation mechanism for electrically generated exciplexes in a carbazole–pyridine copolymer

Although carbazole‐containing copolymers are frequently used as hole‐transporting host materials for polymer organic light‐emitting diodes (OLEDs), they often suffer from the formation of undesired exciplexes when the OLED is operated. The reason why exciplexes sometimes form for electrical excitation, yet not for optical excitation is not well understood. Here, we use luminescence measurements and quantum chemical calculations to investigate the mechanism of such exciplex formation for electrical excitation (electroplex formation) in a carbazole–pyridine copolymer. Our results suggest that the exciplex is formed via a positively charged interchain precursor complex. This complex is stabilized by interactions that involve the nitrogen lone pairs on both chain segments. © 2011 Wiley Periodicals, Inc. J Polym Sci Part B: Polym Phys, 2012     

Auxiliary-field Monte Carlo methods

I discuss Monte Carlo algorithms for quantum many-body systems that employ an auxiliary field to linearize a two-body interaction. These reduce the evaluation of the partition function to sampling many one-body evolutions in a fluctuating field. Fermions and bosons are treated on an equal footing. Applications to potential models and to quantum spin systems are discussed. This work was supported in part by the National Science Foundation, grants PHY82-07332 and PHY85-05682. The potential-model studies were done in collaboration with G. Sugiyama, while A. Khan and T. Troudet were responsible for the work on the quantum spin systems.     

The deconfining phase transition in lattice quantum chromodynamics

We present a large-scale Monte Carlo calculation of the deconfining phase transition temperature in lattice quantum chromodynamics without fermions. Using the Wilson action, the transition temperature as a function of the lattice couplingg is consistent with scaling behavior dictated by the perturbativeα function for 6/g²>6.15. Speaker at the conference; on leave from CRIP, Budapest.     

Density functional theory for a model of nonuniform liquid metal in partially ionized states

Summary The problem of the electronic, ionic and atomic density profiles in a nonuniform liquid metal which can locally exist in partially ionized states is examined using the density functional formalism. Ions and electrons are allowed to bind into atoms through a ?reaction? governed by the mass action law. Formally exact equations for the density profiles are given in terms of the inverse response matrix of the nonuniform system, which consists of two terms: the first corresponding to to a mixture of ions, electrons and structureless atoms and the other to the atomic internal degrees of freedom. Approximate schemes are proposed for both contributions, stressing, in partieular, i) how ionization of the atoms arises with increasing density and the relation with Mott’s criterion for the metal-insulator transition, and ii) the usefulness of a weak-coupling assumption for interspecies correlations. This formalism used together with properly parametrized trial functions for the density profiles should be particularly useful for studying the liquid-vapour interface of alkali metals.

---

Riassunto Il lavoro usa il formalismo del funzionale di densità per discutere la determinazione dei profili di densità in un fluido non omogeneo che può trovarsi localmente in stati di ionizzazione parziale. Con riferimento specifico ai metalli alcalini, la formazione di atomi per legame di ioni ed electtroni è descritta come una ?reazione? governata dalla legge di azione di massa. Le condizioni di equilibrio microscopico del fluido sono espresse tramite una matrice di risposta in cui appaiono due contributi, associati rispettivamente ai gradi di libertà interni degli atomi e ad una miscela di tre specie di particelle senza struttura interna. Si propongono quindi schemi approssimati per il calcolo di questi due contributi, con attenzione particolare all’uso di teorie perturbative e alla relazione tra grado di ionizzazione locale e densità localle, in connessione col criterio di Mott per la transizione isolante-metallo. Il formalismo proposto è in particolare appropriato per lo studio dell’interfaccia liquido-vapore in metalli alcalini.

---

Резюме Используя функционала плотности, исследуется проблема профилей электронной, ионной и атомой ллотностей В неоднодном зидком металле, которий мозет локалщно существоватщ в частично иониэированных состояних. Ионы и электроны могут şвяэыватщся в атомщ череэ ?реакцию, определяемую эаконом дейşтвуюших масс. Приводятся формалщно точные уравнения для профнлеи плотности в термина⇆ обратной матрици отклика для неоднородной системы, которая состоит иэ двух чуленов: первий соответствует ссмеси ионов, электронов и бесстрктурных атмов и второй член соответствует атомным внутренним степеням свобды. Предлагаются приближенные схемы для обоых вкладов, обрашая особое бнмание, в частности, 1) как иониэация атомов воэликает бри увеличени влотности, на свяэы с критерием Мота для берехода ?металл-иеолятор?, и 2) на полеэносты предположения слабой свяэи для межвидовых кореляций. Предложенный Формалиэм, исполыеовалный вместе с параметриэованными пробными функциями для профилей плотнорти, окаэываетця оробенне полеэным для исследования грраницы ?жидкостъ-пар? в шелочлых металлах.

     

Zn1-xCdxSe-ZnSe多量子阱的光学双稳态

用常压MOCVD法在GaAs衬底上生长了Zn_1-xCd_xSe-ZnSe多层结构.通过X-射线衍射谱和光致发光等方法判断,表明该材料为多量子阱结构.从室温下的透射光谱上可以观察到这种多量子阱中的n=1的激子吸收峰,并观测到起因子激子的ns量级的光学双稳态.     

Thermal helium clusters at 3.2 Kelvin in classical and semiclassical simulations

The thermodynamic stability of⁴He_4–13 at 3.2 K is investigated with the classical Monte Carlo method, with the semiclassical path-integral Monte Carlo (PIMC) method, and with the semiclassical all-order many-body method. In the all-order many-body simulation the dipole-dipole approximation including short-range correction is used. The resulting stability plots are discussed and related to recent TOF experiments by Stephens and King. It is found that with classical Monte Carlo of course the characteristics of the measured mass spectrum cannot be resolved. With PIMC, switching on more and more quantum mechanics. by raising the number of virtual time steps results in more structure in the stability plot, but this did not lead to sufficient agreement with the TOF experiment. Only the all-order many-body method resolved the characteristic structures of the measured mass spectrum, including magic numbers. The result shows the influence of quantum statistics and quantum mechanics on the stability of small neutral helium clusters.