Antonino Polimeno

Integrated computational strategies for UV/vis spectra of large molecules in solution

In recent years, the margin of interaction between computational chemistry and most branches of experimental chemistry has increased at a fast pace. The experimental characterization of new systems relies on computational methods for the rationalization of structural, energetic, electronic and dynamical features. In particular, novel computational approaches allow accurate estimates of molecular parameters from spectroscopic optical observables, giving rise to synergic interactions between experimentalists and theoretically-oriented chemists. Our main objective in this tutorial review is to delineate the degree of advancement of possible integrated computational approaches to the interpretation of optical spectroscopies, with an accent on large molecules in solvated environments, based on the combination of advanced quantum mechanical treatments and stochastic modelling of relaxation processes.

Structural dynamics of bio-macromolecules by NMR: The slowly relaxing local structure approach

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A 250 GHz ESR study of o-terphenyl: Dynamic cage effects above Tc

see front matter 2010 Elsevier B.V. A doi:10.1016/j.pnmrs.2010.03.002 Abbreviations: AK, adenylate kinase; AKeco, adeny anisotropy; 3D GAF, 3-dimensional Gaussian axial fluc resonance; FPK, Fokker–Planck–Kramers; GB3, the B headpiece subdomain protein; iRED, isotropic reorien free; MOMD, microscopic order macroscopic disorde Overhauser enhancement; PCA, principal component a L; RDC, residual dipolar coupling; RNA, ribonucleic ac * Corresponding author. Tel.: +972 3 5318049; fax ** Corresponding author. *** Corresponding author. E-mail addresses: eva@nmrsgi5.ls.biu.ac.il (E. Meirov 2010 Elsevier B.V. All rights reserved.

Toward an integrated computational approach to CW-ESR spectra of free radicals

Three nitroxide spin probes of different sizes and geometrical shape were used in a 250 GHz ESR study of the probe rotational dynamics in the fragile glass former ortho-terphenyl (OTP) over a wide temperature range from 380 to 180 K. Comparative studies at 9.5 GHz have also been performed. Perdeuterated 2,2′,6,6′-tetramethyl-4-methyl aminopiperidinyl-N-oxide (MOTA), and 3,3-dimethyloxazolidinyl-N-oxy-2′,3-5α-cholestane (CSL) are, respectively, comparable in size to and larger than the OTP host molecule, whereas Perdeuterated 2,2′,6,6′-tetramethyl-4-piperidine-N-oxide (PDT) is substantially smaller. The sensitivity of 250 GHz ESR to the details of the rotational tumbling for T≳Tc (where Tc is the crossover temperature) was exploited to show that the relaxation is fit by a model that is characteristic of a homogeneous liquid. A nonlinear least-squares analysis shows that below the melting point, Tm, CSL, and MOTA dynamics are well-described by a model of dynamic cage relaxation proposed by Polimeno and Free...

A dissipative particle dynamics description of liquid-crystalline phases. I. Methodology and applications

Interpretation of structural properties and dynamic behaviour of molecules in solution is of fundamental importance to understand their stability, chemical reactivity and catalytic action. Information can be gained, in principle, by a variety of spectroscopic techniques, magnetic as well as optical. In particular, continuous wave electron spin resonance (CW-ESR) measurements are highly informative. However, the wealth of structural and dynamic information which can be extracted from ESR spectroscopy is, at present, limited by the necessity of employing computationally efficient models, which are increasingly complex as they need to take into account diverse relaxation processes affecting the spectrum. In this paper, we address the basic theoretical tools needed to predict, essentially ab initio, CW-ESR spectra observables according to the stochastic Liouville equation (SLE) approach, combined with quantum mechanical and hybrid methods for the accurate and efficient computation of structural, spectroscopic and magnetic properties of molecular systems. We shall discuss, on one hand, the quantum mechanical calculation of magnetic observables, via density functional theory (DFT), time-dependent DFT (TD-DFT) and application of the polarizable continuum model (PCM) for the description of environmental effects, including anisotropic environments and systems where different regions are characterized by different dielectric constants. One the other hand, the explicit evaluation of dynamical effects will be discussed based on the numerically exact treatment of the SLE in the presence of several relaxation processes, which has been proven to be a challenging task.

General Theoretical/Computational Tool for Interpreting NMR Spin Relaxation in Proteins

Simulations of nematic and smectic mesophases based on a dissipative particle dynamics approach are discussed. Mesogenic units are built in the form of standard semirigid bead-spring chains. It is shown that nematic phases can be formed for chains containing at least eight beads, provided that the conservative soft-repulsive potential between nonconnected beads is sufficiently strong. Smectic phases are observed only by modifying the repulsive interaction between the main-chain and terminal beads. The simulations indicate that the smectic-nematic and smectic-isotropic phase transitions take place through the buckling of the smectic layering in the system.

Multivariate diffusion models of dielectric friction and TICT transitions

We developed in recent years the slowly relaxing local structure (SRLS) approach for analyzing NMR spin relaxation in proteins. SRLS is a two-body coupled rotator model which accounts rigorously for mode-coupling between the global motion of the protein and the local motion of the spin-bearing probe and allows for general properties of the second rank tensors involved. We showed that a general tool of data analysis requires both capabilities. Several important functionalities were missing in our previous implementations of SRLS in data fitting schemes, and in some important cases, the calculations were tedious. Here we present a general implementation which allows for asymmetric local and global diffusion tensors, distinct local ordering and local diffusion frames, and features a rhombic local potential which includes Wigner matrix element terms of ranks 2 and 4. A recently developed hydrodynamics-based approach for calculating global diffusion tensors has been incorporated into the data-fitting scheme. The computational efficiency of the latter has been increased significantly through object-oriented programming within the scope of the C++ programming language, and code parallelization. A convenient graphical user interface is provided. Currently autocorrelated (15)N spin relaxation data can be analyzed effectively. Adaptation to any autocorrelated and cross-correlated relaxation analysis is straightforward. New physical insight is gleaned on largely preserved local structure in solution, even in chain segments which experience slow local motion. Prospects associated with improved dynamic models, and new applications made possible by the current implementation of SRLS, are delineated.

Rotational dynamics of axially symmetric solutes in isotropic solvents. II. The stochastic model

A multidimensional diffusional approach is proposed to describe rotational diffusion or conformational transitions in molecular systems in the presence of coupling with polar solvent coordinates. The model is applied to interpret dielectric friction effects and Twisted Intramolecular Charge Transfer (TICT) kinetics. Full numerical solutions are compared with those obtained by approximate procedures.

Selenocysteine oxidation in glutathione peroxidase catalysis: an MS-supported quantum mechanics study

In paper I of this series, a molecular dynamics (MD) study of liquid chlorine was performed, and it includes the definition and observation of operational cage variables. These cage variables were used to describe the local environment of a rotating axially symmetric molecule, or probe. Probe and cage properties of interest, such as rotational correlation functions and momentum correlation functions, were computed, together with an effective distribution of librational cage frequencies. In the second part of this work, we develop a stochastic model which includes the relevant elementary relaxation processes previously identified by the MD study. This stochastic model is based upon a multi‐dimensional Fokker–Planck equation for the coupled dynamics of the probe and cage orientations, the angular momentum of the probe, and the librational frequencies for the probe in the cage. Semi‐analytical approximations, based upon a ‘‘Born–Oppenheimer’’‐type separability of fast and slow variables, are used in order to...

Hydrodynamic modeling of diffusion tensor properties of flexible molecules.

Glutathione peroxidases (GPxs) are enzymes working with either selenium or sulfur catalysis. They adopted diverse functions ranging from detoxification of H(2)O(2) to redox signaling and differentiation. The relative stability of the selenoenzymes, however, remained enigmatic in view of the postulated involvement of a highly unstable selenenic acid form during catalysis. Nevertheless, density functional theory calculations obtained with a representative active site model verify the mechanistic concept of GPx catalysis and underscore its efficiency. However, they also allow that the selenenic acid, in the absence of the reducing substrate, reacts with a nitrogen in the active site. MS/MS analysis of oxidized rat GPx4 complies with the predicted structure, an 8-membered ring, in which selenium is bound as selenenylamide to the protein backbone. The intermediate can be re-integrated into the canonical GPx cycle by glutathione, whereas, under denaturing conditions, its selenium moiety undergoes β-cleavage with formation of a dehydro-alanine residue. The selenenylamide bypass prevents destruction of the redox center due to over-oxidation of the selenium or its elimination and likely allows fine-tuning of GPx activity or alternate substrate reactions for regulatory purposes.