Pairwise decomposition of residue interaction energies using semiempirical quantum mechanical methods in studies of protein-ligand interaction

Pairwise decomposition of the interaction energy between molecules is shown to be a powerful tool that can increase our understanding of macromolecular recognition processes. Herein we calculate the pairwise decomposition of the interaction energy between the protein human carbonic anhydrase II (HCAII) and the fluorine-substituted ligand N-(4-sulfamylbenzoyl)benzylamine (SBB) using semiempirical quantum mechanics based methods. We dissect the interaction between the ligand and the protein by dividing the ligand and the protein into subsystems to understand the structure-activity relationships as a result of fluorine substitution. In particular, the off-diagonal elements of the Fock matrix that is composed of the interaction between the ionic core and the valence electrons and the exchange energy between the subsystems or atoms of interest is examined in detail. Our analysis reveals that the fluorine-substituted benzylamine group of SBB does not directly affect the binding energy. Rather, we find that the strength of the interaction between Thr199 of HCAII and the sulfamylbenzoyl group of SBB affects the binding affinity between the protein and the ligand. These observations underline the importance of the sulfonamide group in binding affinity as shown by previous experiments (Maren, T. H.; Wiley: C. E. J. Med. Chem. 1968, 11, 228-232). Moreover, our calculations qualitatively agree with the structural aspects of these protein-ligand complexes as determined by X-ray crystallography.     

A short synthesis of the β-amyloid (Aβ) aggregation inhibitor 3-p-Toluoyl-2-[4′-(3-diethylaminopropoxy)-phenyl]-benzofuran

A short and convenient synthesis of 3-p-toluoyl-2-[4′-(3-diethylaminopropoxy)-phenyl]-benzofuran, an inhibitor of the aggregation of β-amyloid, which is thought to be the underlying cause of Alzheimer's disease, is described.     

On the Spectra of Left-Definite Operators

If A is a self-adjoint operator that is bounded below in a Hilbert space H, Littlejohn and Wellman (J Diff Equ 181(2):280–339, 2002) showed that, for each r > 0, there exists a unique Hilbert space H _r and a unique self-adjoint operator A _r in H _r satisfying certain conditions dependent on H and A. The space H _r and the operator A _r are called, respectively, the rth left-definite space and rth left-definite operator associated with (H, A). In this paper, we show that the operators A, A _r , and A _s (r, s > 0) are isometrically isomorphically equivalent and that the spaces H, H _r , and H _s (r, s > 0) are isometrically isomorphic. These results are then used to reproduce the left-definite spaces and left-definite operators. Furthermore, we will see that our new results imply that the spectra of A and A _r are equal, giving us another proof of this phenomenon that was first established in Littlejohn and Wellman (J Diff Equ 181(2):280–339, 2002).     

Classical and Sobolev orthogonality of the nonclassical Jacobi polynomials with parameters \alpha =\beta =-1

In this paper, we consider the second-order differential expression $$\begin{aligned} \ell [y](x)=(1-x^{2})(-(y^{\prime }(x))^{\prime }+k(1-x^{2})^{-1} y(x))\quad (x\in (-1,1)). \end{aligned}$$ This is the Jacobi differential expression with nonclassical parameters $\alpha =\beta =-1$ in contrast to the classical case when $\alpha ,\beta >-1$ . For fixed $k\ge 0$ and appropriate values of the spectral parameter $\lambda ,$ the equation $\ell [y]=\lambda y$ has, as in the classical case, a sequence of (Jacobi) polynomial solutions $\{P_{n}^{(-1,-1)} \}_{n=0}^{\infty }.$ These Jacobi polynomial solutions of degree $\ge 2$ form a complete orthogonal set in the Hilbert space $L^{2}((-1,1);(1-x^{2})^{-1})$ . Unlike the classical situation, every polynomial of degree one is a solution of this eigenvalue equation. Kwon and Littlejohn showed that, by careful selection of this first-degree solution, the set of polynomial solutions of degree $\ge 0$ are orthogonal with respect to a Sobolev inner product. Our main result in this paper is to construct a self-adjoint operator $T$ , generated by $\ell [\cdot ],$ in this Sobolev space that has these Jacobi polynomials as a complete orthogonal set of eigenfunctions. The classical Glazman–Krein–Naimark theory is essential in helping to construct $T$ in this Sobolev space as is the left-definite theory developed by Littlejohn and Wellman.     

Science Conference Presenters’ Images of Inquiry

Inquiry‐focused professional development and conceptions of inquiry held by eight professional development leaders were investigated within the context of a state science teacher conference. The prominent session format involved session leaders modeling classroom experiences. In all sessions, classroom inquiry was portrayed as a teacher‐guided activity with the primary goal being to increase motivation for engaging students in classroom inquiry. The leaders’ conceptualized inquiry primarily as a teaching approach with various goals, characteristics, and potential barriers. The findings of this study provide evidence of how inquiry, a prominent feature of science education reform, was portrayed in sessions at a conference sponsored by a state affiliate of the National Science Teachers Association and thought about by persons who led these sessions. The findings have implications for teacher learning from conference‐based professional development and its potential influence on science teacher thinking and practice.     

Towards a Comprehensive Stability Theory for Feynman’s Operational Calculus: The Time-Dependent Setting

We obtain lower bounds on blow-up of solutions for the 3D magneto-micropolar equations. More precisely, we establish some estimates for the solution \((\mathbf{u},\mathbf{w},\mathbf{b}) (t)\) in its maximal interval \([0,T^{*})\) provided that \(T^{*}<\infty\), which show for \(\delta\in(0,1)\) that \(\|(\mathbf{u},\mathbf{w},\mathbf{b})(t)\|_{\dot{H}^{s}}\) is at least of the order \((T^{*}-t)^{-(\delta s)/(1+2\delta)}\) for \(s\geq1/2+\delta\). In particular, by choosing a suitable \(\delta\), one concludes that \(\|(\mathbf{u},\mathbf{w},\mathbf{b})(t)\|_{\dot{H}^{s}}\) is at least of the order \((T^{*}-t)^{-s/4}\), and \((T^{*}-t)^{1/4-s/2}\) for \(s\geq1\), and \(1/2< s<3/2\), respectively. We also show that \((T^{*}-t)^{-s/3}\) is a lower rate for \(\|(\mathbf{u},\mathbf{w},\mathbf{b})(t)\|_{\dot{H}^{s}}\) if \(s>3/2\).     

Controllability of linear systems,differential geometry curves in grassmannians and generalized grassmannians,and riccati equations

We study the linear system =Ax+Bu from a differential geometric point of view. It is well-known that controllability of the system is related to the one-parameter family of operators e^t B. We use this to give a proof of the classical controllability conditions in terms of the differential geometry of certain curves in ⁿ. We then view (t)=Im(e^t B) as a curve in appropriate Grassmannian and see that, in local coordinates, is an integral curve of the flow induced by a matrix Riccati equation. We obtain qualitative geometric conditions on that are equivalent to the controllability of the system. To get quantitiative results, we lift to a curve l' in a splitting space, a generalized Grassmannian, which has the advantage of being a reductive homogeneous space of the general linear group, GL(ⁿ). Explicit and simple expressions concerning the geometry of are computed in terms of the Lie algebra of GL(ⁿ), and these are related to the controllability of the system.James Wolper was a visiting professor in the Department of Mathematics at Texas Tech University while much of this research was conducted. He would like to express appreciation for the hospitality he received during his visit.     

Stability Properties of Feynman's Operational Calculus for Exponential Functions of Noncommuting Operators

Stability properties of Feynman's operational calculus are addressed in the setting of exponential functions of noncommuting operators. Applications of some of the stability results are presented. In particular, the time-dependent perturbation theory of nonrelativistic quantum mechanics is presented in the setting of the operational calculus and application of the stability results of this paper to the perturbation theory are discussed.     

On the origin of the ferromagnetism in Zn0.8Mn0.2O having a higher Curie temperature than Zn0.8Co0.2O

Zn_0.8Co_0.2O and Zn_0.8Mn_0.2O films were deposited on substrates by a sol–gel technique. X-ray diffraction, field-emission scanning electron microscopy, photoluminescence, and ferromagnetism measurements were used to characterize these dilute magnetic semiconductors. It is shown that the ferromagnetic properties might be related to the formation of acceptor-like defects in the Zn_0.8Co_0.2O and Zn_0.8Mn_0.2O films. It is found that ferromagnetic Zn_0.8Mn_0.2O has a higher Curie temperature than Zn_0.8Co_0.2O. In addition, the higher ratio of grain-boundary area to grain volume of Zn_0.8Mn_0.2O than Zn_0.8Co_0.2O indicates that grain boundaries and related acceptors are the intrinsic origin for ferromagnetism.