Flexible protein regions containing cationic and aromatic side-chains exposed to solvent may form transient cation-π interactions with structural and functional roles. To evaluate their stability and identify important intramolecular cation-π contacts, a combination of free energy profiles estimated from umbrella sampling with molecular dynamics simulations and chemical shift perturbations (CSP) obtained from NMR experiments is applied here to the complete catalytic domain of human phosphatase Cdc25B. This protein is a good model system for transient cation-π interactions as it contains only one Trp residue (W550) in the disordered Cterminal segment and a total of 17 Arg residues, many exposed to solvent. Eight putative Arg-Trp pairs were simulated here. Only R482 and R544 show bound profiles corresponding to important transient cation-π interactions, while the others have dissociative or almost flat profiles. These results are corroborated by CSP analysis of three Cdc25B point mutants (W550A, R482A and R544A) disrupting cation-π contacts. The proposed validation of statistically representative molecular simulations by NMR spectroscopy could be applied to identify transient contacts of proteins in general but carefully, as NMR chemical shifts are sensitive to changes in both molecular contacts and conformational distributions.

Flexible protein regions containing cationic and aromatic side-chains exposed to solvent may form transient cation-π interactions with structural and functional roles. To evaluate their stability and identify important intramolecular cation-π contacts, a combination of free energy profiles estimated from umbrella sampling with molecular dynamics simulations and chemical shift perturbations (CSP) obtained from NMR experiments is applied here to the complete catalytic domain of human phosphatase Cdc25B. This protein is a good model system for transient cation-π interactions as it contains only one Trp residue (W550) in the disordered Cterminal segment and a total of 17 Arg residues, many exposed to solvent. Eight putative Arg-Trp pairs were simulated here. Only R482 and R544 show bound profiles corresponding to important transient cation-π interactions, while the others have dissociative or almost flat profiles. These results are corroborated by CSP analysis of three Cdc25B point mutants (W550A, R482A and R544A) disrupting cation-π contacts. The proposed validation of statistically representative molecular simulations by NMR spectroscopy could be applied to identify transient contacts of proteins in general but carefully, as NMR chemical shifts are sensitive to changes in both molecular contacts and conformational distributions.

O presente artigo busca debater, sob a luz das novas dinâmicas do capitalismo que se impõem desde a década de 1970, as transformações ocorridas nas centralidades intra-urbanas da metrópole de São Paulo. Adotando o complexo corporativo metropolitano e uma proposta de delimitação do já amplamente estudado Setor Sudoeste como instrumentos de análise, são estudadas as transformações do setor Chucri Zaidan da operação urbana Água Espraiada, como expressão limítrofe do novo centro. Torna-se então possível, realizando uma mediação com a conjuntura econômica, política e sanitária que se desenha, refletir sobre potenciais desdobramentos, dadas as condições geográficas estabelecidas.