Importance of solvent accessibility and contact surfaces in modeling side-chain conformations in proteins

Contact surface area and chemical properties of atoms are used to concurrently predict conformations of multiple amino acid side chains on a fixed protein backbone. The combination of surface complementarity and solvent-accessible surface accounts for van der Waals forces and solvation free energy. The scoring function is particularly suitable for modeling partially buried side chains. Both iterative and stochastic searching approaches are used. Our programs (Sccomp-I and Sccomp-S), with relatively fast execution times, correctly predict chi1 angles for 92-93% of buried residues and 82-84% for all residues, with an RMSD of approximately 1.7 A for side chain heavy atoms. We find that the differential between the atomic solvation parameters and the contact surface parameters (including those between noncomplementary atoms) is positive; i.e., most protein atoms prefer surface contact with other protein atoms rather than with the solvent. This might correspond to the driving force for maximizing packing of the protein. The influence of the crystal packing, completeness of rotamer library and precise positioning of Cbeta atoms on the accuracy of side-chain prediction are examined. The Sccomp-S and Sccomp-I programs can be accessed through the Web (http://sgedg.weizmann.ac.il/sccomp.html) and are available for several platforms.     

CO2 activation by metal−ligand-cooperation mediated by iridium pincer complexes

Abstract

Herein we report the reversible activation of CO₂ by the dearomatized complex [(^tBuPNP*)Ir(COE)] (1) and by the aromatized complex [(^tBuPNP)Ir(C₆H₅)] (2) via metal-ligand cooperation (MLC) (^tBuPN = 2,6-bis-(di-tert-butylphosphinomethyl)pyridine; ^tBuPNP* = deprotonated PNP; COE = cyclooctadiene). The [1,3]-addition of CO₂ to 1 and 2 is reversible at ambient temperature. While the dearomatized complex 1 reacts readily at ambient temperature with CO₂ in THF or benzene, complex 2 reacts with CO₂ upon heating in benzene at 80 °C or at ambient temperature in THF. The novel aromatized complex [(^tBuPNP)IrCl] (10) does not react with CO₂. Based on the reactivity patterns of 1, 2, and 10 with CO₂, we suggest that CO₂ activation via MLC takes place only via the dearomatized species, and that in the case of 2 THF plays a role as a polar solvent in facilitating formation of the dearomatized hydrido phenyl complex intermediate (complex II).     

Hybrid liquid membrane (HLM) system in separation technologies

A novel liquid membrane system, denoted hybrid liquid membrane (HLM), was developed for the separation of solutes (metal ions, acids, etc.). It utilizes a solution of an extracting reagent (carrier solution), flowing between membranes. The membranes, which separate the carrier solution from feed and receiving (strip) solutions, enable the transport of solutes, but block the transfer of the carrier to the feed or to the strip. Blocking the carrier is achieved through membranes hydrophilic/hydrophobic or ion exchange properties, or through their rentention abilities, due to pore size.     

Backbone-assisted reactions of polymers. V. Kinetics of isomerization of poly(chloromethylthiirane) and poly(3-chlorothietane) in solution

The reversible isomerization of poly(chloromethylthiirane) and poly(3-chlorothietane) represents a new kind of polymer reaction and a new method of copolymer synthesis. In chloroform, in dichloromethane, or in nitrobenzene the reaction is well described by reversible first-order kinetics. A rate increase of ca. 40% on changing the solvent from chloroform to nitrobenzene is consistent with an isomerization mechanism that involves a rate-determining attack of the backbone sulfur atom on the neighboring carbon-chlorine bond and rapid ring-opening of the thiiranium ion intermediate by chloride ion.     

The Nakamura Theorem for coalition structures of quota games

This paper considers a model of society $S$ with a finite number of individuals,n, a finite set off alternatives, Ω effective coalitions that must contain ana priori given numberq of individuals. Its purpose is to extend the Nakamura Theorem (1979) to the quota games where individuals are allowed to form groups of sizeq which are smaller than the grand coalition. Our main result determines the upper bound on the number of alternatives which would guarantee, for a given e andq, the existence of a stable coalition structure for any profile of complete transitive preference relations. Our notion of stability, $S$ -equilibrium, introduced by Greenberg-Weber (1993), combines bothfree entry andfree mobility and represents the natural extension of the core to improper or non-superadditive games where coalition structures, and not only the grand coalition, are allowed to form.     

Development of nanostructure in resistant starch type III during thermal treatments and cycling

The effect of recrystallization temperature on the lamellar structure of RSIII samples was studied using XRD and SAXS. The polymorph type could be manipulated in a controlled manner, independently of the plant source. In RSIII from corn starch and from high-amylose corn starch, retrogradation at a low temperature led to the formation of polymorph B with lamellas arranged in long-range periodicity, whereas retrogradation at a high temperature led to the formation of polymorphs A and V with no defined periodicity. The retrogradation temperature of wheat starch did not have a major effect on its nanostructure. For both polymorphs, the enzymatic degradation decreased as the degree of order within the crystal increased.     

Identification of SARS-CoV-2 Receptor Binding Inhibitors by In Vitro Screening of Drug Libraries

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the coronavirus disease 2019 (COVID-19) global pandemic. The first step of viral infection is cell attachment, which is mediated by the binding of the SARS-CoV-2 receptor binding domain (RBD), part of the virus spike protein, to human angiotensin-converting enzyme 2 (ACE2). Therefore, drug repurposing to discover RBD-ACE2 binding inhibitors may provide a rapid and safe approach for COVID-19 therapy. Here, we describe the development of an in vitro RBD-ACE2 binding assay and its application to identify inhibitors of the interaction of the SARS-CoV-2 RBD to ACE2 by the high-throughput screening of two compound libraries (LOPAC^®1280 and DiscoveryProbeTM). Three compounds, heparin sodium, aurintricarboxylic acid (ATA), and ellagic acid, were found to exert an effective binding inhibition, with IC50 values ranging from 0.6 to 5.5 µg/mL. A plaque reduction assay in Vero E6 cells infected with a SARS-CoV-2 surrogate virus confirmed the inhibition efficacy of heparin sodium and ATA. Molecular docking analysis located potential binding sites of these compounds in the RBD. In light of these findings, the screening system described herein can be applied to other drug libraries to discover potent SARS-CoV-2 inhibitors.     

Integral generators for the cohomology ring of moduli spaces of sheaves over Poisson surfaces

Let M be a smooth and compact moduli space of stable coherent sheaves on a projective surface S with an effective (or trivial) anti-canonical line bundle. We find generators for the cohomology ring of M, with integral coefficients. When S is simply connected and a universal sheaf E exists over S×M, then its class [E] admits a Künneth decomposition as a class in the tensor product of the topological K-rings. The generators are the Chern classes of the Künneth factors of [E] in . The general case is similar.     

2 kW, M2 < 10 radially polarized beams from aberration-compensated rod-based Nd:YAG lasers

Radially polarized light in a 2.1 kW, good quality beam was obtained from a Nd:YAG rod-based master oscillator power amplifier. Several techniques were utilized: a pure radially polarized oscillator, efficient pump chambers, external compensation of lower-order aberrations, and higher-order aberration compensation by pairing of pump chambers.     

Plasmon-soliton

Formation of a novel hybrid-vector spatial plasmon-soliton in a Kerr slab embedded between metal plates is predicted and analyzed with a modified nonlinear Schrodinger equation encompassing hybrid-vector field characteristics. Assisted by the transverse plasmonic effect, the self-trapping dimension of the plasmon-soliton was substantially compressed (compared with the dielectrically cladded slab case) when reducing the slab width. The practical limitation of the plasmon-soliton size reduction is determined by available nonlinear materials and metal loss. For the extreme reported values of nonlinear index change, we predict a soliton with a cross section of 300 nm x 30 nm (average dimension of 100 nm).