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

On localized solutions of an equation governing Benard-Marangoni convection

Provided here is numerical evidence of localized solutions, solitary waves, in a model equation for Bénard convection driven by interfacial stresses (Marangoni effect).This research has been supported by Grant 1052 of the Bulgarian Ministry of Science and Higher Education and by CICYT (Spain) under Grants PB 86-65 1 and PB-90-264

Theory of Ion-Transfer Processes at Electrodes and Solution

An extensive review is given of the author\u27s theory of ion- transfer processes at electrodes and in solution. The exposition concerns only those features which are independent of any assumptions about the mechan1sm of the particular process. The theory allows extension to many specific cases by adoption of simple models

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

Granulomatosis with polyangiitis mimicking infective endocarditis in an adolescent male

Granulomatosis with polyangiitis (GPA) is a rare but serious small vessel vasculitis with heterogeneous clinical presentation ranging from mainly localised disease with a chronic course, to a florid, acute small vessel vasculitic form characterised by severe pulmonary haemorrhage and/or rapidly progressive vasculitis or other severe systemic vasculitic manifestations. Cardiac involvement is, however, uncommon in the paediatric population. We report a case of a 16-year-old male who presented with peripheral gangrene and vegetation with unusual location on the supporting apparatus of the tricuspid valve, initially considered to have infective endocarditis but ultimately diagnosed with GPA. We provide an overview of the limited literature relating to cardiac involvement in GPA, and the diagnostic challenge relating to infective endocarditis in this context, especially focusing on the interpretation of the antineutrophil cytoplasmic antibody (ANCA) and the characteristic clinical features to identify in order to promptly recognise GPA, since timely diagnosis and treatment are essential for this potentially life-threatening condition

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.

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