Conformational effects on the Circular Dichroism of Human Carbonic Anhydrase II: a multilevel computational study

Circular Dichroism (CD) spectroscopy is a powerful method for investigating conformational changes in proteins and therefore has numerous applications in structural and molecular biology. Here a computational investigation of the CD spectrum of the Human Carbonic Anhydrase II (HCAII), with main focus on the near-UV CD spectra of the wild-type enzyme and it seven tryptophan mutant forms, is presented and compared to experimental studies. Multilevel computational methods (Molecular Dynamics, Semiempirical Quantum Mechanics, Time-Dependent Density Functional Theory) were applied in order to gain insight into the mechanisms of interaction between the aromatic chromophores within the protein environment and understand how the conformational flexibility of the protein influences these mechanisms. The analysis suggests that combining CD semi empirical calculations, crystal structures and molecular dynamics (MD) could help in achieving a better agreement between the computed and experimental protein spectra and provide some unique insight into the dynamic nature of the mechanisms of chromophore interactions

Weak electricity of the Nucleon in the Chiral Quark-Soliton Model

The induced pseudotensor constant (weak electricity) of the nucleon is calculated in the framework of the chiral quark soliton model. This quantity originates from the G-parity violation and hence is proportional to $m_u-m_d$. We obtain for $m_u-m_d=-5 MeV$ a value of $g_T/g_A =-0.0038$.Comment: The final version. Accepted for publication in Phys. Rev.

Stretching and folding versus cutting and shuffling: An illustrated perspective on mixing and deformations of continua

We compare and contrast two types of deformations inspired by mixing applications -- one from the mixing of fluids (stretching and folding), the other from the mixing of granular matter (cutting and shuffling). The connection between mechanics and dynamical systems is discussed in the context of the kinematics of deformation, emphasizing the equivalence between stretches and Lyapunov exponents. The stretching and folding motion exemplified by the baker's map is shown to give rise to a dynamical system with a positive Lyapunov exponent, the hallmark of chaotic mixing. On the other hand, cutting and shuffling does not stretch. When an interval exchange transformation is used as the basis for cutting and shuffling, we establish that all of the map's Lyapunov exponents are zero. Mixing, as quantified by the interfacial area per unit volume, is shown to be exponentially fast when there is stretching and folding, but linear when there is only cutting and shuffling. We also discuss how a simple computational approach can discern stretching in discrete data.Comment: REVTeX 4.1, 9 pages, 3 figures; v2 corrects some misprints. The following article appeared in the American Journal of Physics and may be found at http://ajp.aapt.org/resource/1/ajpias/v79/i4/p359_s1 . Copyright 2011 American Association of Physics Teachers. This article may be downloaded for personal use only. Any other use requires prior permission of the author and the AAP

Conformational flexibility influences structure–function relationships in tyrosyl protein sulfotransferase-2

Tyrosine sulfation is a very important posttranslational modification of proteins. It is catalyzed by tyrosylprotein sulfotransferase and recently became increasingly important for biomedicine and pharmacy. An important insight about structure–activity relationships of human tyrosylprotein sulfotransferase has been received by elucidating the crystal structure, but there is still no understanding about how conformational flexibility and dynamics which are fundamental protein properties influence structure–function relationships of the enzyme. In order to provide this missing but crucially important knowledge we performed a comprehensive atomistic molecular dynamics study which revealed that (i) the conformational flexibility influences sensitively key structural determinants and interactions between the enzyme, the substrate and the cofactor; (ii) a more open conformation adopted by the substrate for binding in TPST 2; (iii) the mutations of key residues related with catalysis and binding change alter the enzyme structure and influence important interactions between the enzyme, the cofactor and the substrate

How does conformational flexibility influence key structural features involved in activation of anaplastic lymphoma kinase?

Anaplastic Lymphoma Kinase (ALK) plays a major role in developing tumor processes and therefore has emerged as a validated therapeutic target. Applying atomistic molecular dynamics simulations on the wild type enzyme and the nine most frequently occurring and clinically important activation mutants we revealed important conformational effects on key interactions responsible for the activation of the enzyme

Self-Consistent Pushing and Cranking Corrections to the Meson Fields of the Chiral Quark-Loop Soliton

We study translational and spin-isospin symmetry restoration for the two-flavor chiral quark-loop soliton. Instead of a static soliton at rest we consider a boosted and rotating hedgehog soliton. Corrected classical meson fields are obtained by minimizing a corrected energy functional which has been derived by semi-classical methods ('variation after projection'). We evaluate corrected meson fields in the region 300 MeV \le M \le 600 MeV of constituent quark masses M and compare them with the uncorrected fields. We study the effect of the corrections on various expectation values of nuclear observables such as the root-mean square radius, the axial-vector coupling constant, magnetic moments and the delta-nucleon mass splitting.Comment: 19 pages, LaTeX, 7 postscript figures included using 'psfig.sty', to appear in Int.J.Mod.Phys.