Protein‐specific force field derived from the fragment molecular orbital method can improve protein–ligand binding interactions

Accurate computational estimate of the protein–ligand binding affinity is of central importance in rational drug design. To improve accuracy of the molecular mechanics (MM) force field (FF) for protein–ligand simulations, we use a protein‐specific FF derived by the fragment molecular orbital (FMO) method and by the restrained electrostatic potential (RESP) method. Applying this FMO‐RESP method to two proteins, dodecin, and lysozyme, we found that protein‐specific partial charges tend to differ more significantly from the standard AMBER charges for isolated charged atoms. We did not see the dependence of partial charges on the secondary structure. Computing the binding affinities of dodecin with five ligands by MM PBSA protocol with the FMO‐RESP charge set as well as with the standard AMBER charges, we found that the former gives better correlation with experimental affinities than the latter. While, for lysozyme with five ligands, both charge sets gave similar and relatively accurate estimates of binding affinities. © 2013 Wiley Periodicals, Inc.     

A Strategy toward Cyclic Topologies Based on the Dynamic Behavior of a Bis(hindered amino)disulfide Linker

A simple and efficient method to generate macrocyclic structures has been developed based on the dynamic behavior of the linker bis(2,2,6,6‐tetramethylpiperidin‐1‐yl)disulfide (BiTEMPS). The prime linear structure was transformed into a (macro)cycle using the following sequence: 1) thiol–ene reaction with a BiTEMPS derivative to afford the linear precursor, then 2) an entropy‐driven transformation induced by diluting and heating. The radicals generated from BiTEMPS upon heating are highly tolerant toward a variety of chemical species, including oxygen and olefins, but they exhibit high reactivity in exchange reactions, which can be applied to the topology transformation of various skeletons. The advantages of the present method, namely, its procedural simplicity and substrate versatility, are demonstrated by the gram‐scale synthesis of cyclic compounds with low and relatively high molecular weight.     

Minimum Polynomial for Single-Mode Parabose Parasupercharge and Hamiltonian

We calculate the minimum polynomial φ(x,y) of parasupercharge Q and Hamiltonian H for single-mode parabose parasupersymmetry (P-PSUSY). Suppose that φ(x,y) satisfies the homogeneity ∀ λ∈ℝ,φ(λ x,λ ² y)=λ ⁿ φ(x,y), then the parafermionic order p _f is restricted to either 1, 2, or 4. Under the P-PSUSY, the homogeneity of the φ(x,y) is equivalent to the parasuperconformality of Q and H. The physical meaning of the parasuperconformality is discussed, in connection with the spin of the elementary particle.     

Ionic diffusion and structural changes in lithium compounds

⁷Li NMR measurements have been performed to study milling effects on ionic diffusion in lithium cobalt oxide, LiCoO₂ and piezoelectric compound, LiNbO₃ prepared by mechanical milling method. The milling process gives quite different effects on NMR spectra of these compounds. Both ⁷Li MAS and static NMR spectra of the milled LiCoO₂ show the line broadening with increasing milling time. ⁵⁹Co static spectra also show specific changes in the line shape with increasing milling time. These results would be attributed to the change in an electronic state of Co 3d orbitals because of charge compensation associated with oxygen vacancies and/or defects. ⁷Li static NMR spectrum of milled LiNbO₃ shows complicated line shape with increasing milling time. It is explained by superposition of two spectra arising from mobile Li⁺ ions and non-mobile ones settled on the fixed site. It is shown that the ratio of mobile Li⁺ ions increases up to a maximum of 9.4% with increasing milling time. Milling effects on the Li⁺ ionic diffusion in LiCoO₂ and LiNbO₃ are discussed in connection with changes in local structure.     

Synthesis and characterization of cyclotetraphosphato complexes of Rh(I), Ir(I), Ru(II), and Pd(II)

The cyclotetraphosphate ion (P(4)O(12)(4)(-)) as a PPN (PPN = (PPh(3))(2)N(+)) salt reacts with [MCl(cod)](2) (M = Rh, Ir; cod = 1,5-cyclooctadiene) to give the dinuclear complexes (PPN)(2)[[M(cod)](2)(P(4)O(12))], in which the two metal moieties are situated trans to each other with respect to the P(4)O(4) ring in the solid state. In solution, however, these complexes exist as mixtures of trans and cis isomers. On the other hand, the P(4)O(12)(4)(-) ion reacts with 4 equiv of [Rh(cod)(MeCN)(x)](+) cation to give the tetranuclear complex [[Rh(cod)](4)(P(4)O(12))], where the four Rh(cod) fragments are bound to the P(4)O(12) platform alternately on both sides of the P(4)O(4) ring. Dinuclear P(4)O(12) complexes of ruthenium and palladium are also synthesized.     

A circular dichroism study of the interaction between<Emphasis Type="Italic"> n</Emphasis>-decanoyl-<Emphasis Type="Italic">N</Emphasis>-methylglucamide and surface active agents in mixed micelles

The interaction between MEGA-10 and surface active agents was studied by means of circular dichroism. The molecular ellipticity of MEGA-10 varied with the addition of surface active agents, but its peak wavelength did not. The carbonyl group of MEGA-10 did not interact with the nonionic surface active agents nor the catanionic surfactant (of which the anionic and cationic portions were decanesulfonate and decyltrimethylammonium, respectively). It did, however, interact with the ionic surfactants, and also strongly with the ammonium group and the benzene ring. The interaction between MEGA-10 and ionic surfactant charges did not differ according to the sign of the charge. Circular dichroism spectra are a useful tool for performing research into the interaction between an optically active carbonyl group and an additive.     

Raman spectra of conducting TCNQ salts; Estimation of the degree of charge transfer from vibrational frequencies

The linear dependency of TCNQ ν₄ frequencies on the formal charge was observed and was attributed to the motional narrowing of the Raman band by hopping of conduction electrons. The formal charges of TTF-TCNQ (0.59) and NMP-TCNQ (0.62) estimated from this dependency agreed well with those from other experiments.     

Acoustically oscillating emission from NO*2 produced by infrared photosensitized reaction in SF6 + NO2

An oscillating time profile was observed in the visible emission of NO^*₂ produced by an infrared photosensitized reaction in NO₂ + SF₆. The origin of the modulation was found to be the periodical heating of NO₂ due to the sound wave generated by the heat released from SF₆ upon infrared multiphoton excitation.     

Computational studies of intramolecular hydrogen atom transfers in the beta-hydroxyethylperoxy and beta-hydroxyethoxy radicals

The beta-hydroxyethylperoxy (I) and beta-hydroxyethoxy (III) radicals are prototypes of species that can undergo hydrogen atom transfer across their intramolecular hydrogen bonds. These reactions may play an important role in both the atmosphere and in combustion systems. We have used density functional theory and composite electronic structure methods to predict the energetics of these reactions, RRKM/master equation simulations to model the kinetics of chemically activated I, and variational transition state theory (TST) to predict thermal rate constants for the 1,5-hydrogen shift in I (Reaction 1) and the 1,4-hydrogen shift in III (Reaction 2). Our multi-coefficient Gaussian-3 calculations predict that Reaction 1 has a barrier of 23.59 kcal/mol, and that Reaction 2 has a barrier of 22.71 kcal/mol. These predictions agree rather well with the MPW1K and BB1K density functional theory predictions but disagree with predictions based on B3LYP energies or geometries. Our RRKM/master equation simulations suggest that almost 50% of I undergoes a prompt hydrogen shift reaction at pressures up to 10 Torr, but the extent to which I is chemically activated is uncertain. For Reaction 1 at 298 K, the variational TST rate constant is approximately 30% lower than the conventional TST result, and the microcanonical optimized multidimensional tunneling (muOMT) method predicts that tunneling accelerates the reaction by a factor of 3. TST calculations on Reaction 2 reveal no variational effect and a 298 K muOMT transmission coefficient of 10(5). The Eckart method overestimates transmission coefficients for both reactions.