Good Quality Of Model Research Articles

A Combined Computational and Functional Approach Identifies New Residues Involved in pH-dependent Gating of ASIC1a

Acid-sensing ion channels (ASICs) are key receptors for extracellular protons. These neuronal nonvoltage-gated Na(+) channels are involved in learning, the expression of fear, neurodegeneration after ischemia, and pain sensation. We have applied a systematic approach to identify potential pH sensors in ASIC1a and to elucidate the mechanisms by which pH variations govern ASIC gating. We first calculated the pK(a) value of all extracellular His, Glu, and Asp residues using a Poisson-Boltzmann continuum approach, based on the ASIC three-dimensional structure, to identify candidate pH-sensing residues. The role of these residues was then assessed by site-directed mutagenesis and chemical modification, combined with functional analysis. The localization of putative pH-sensing residues suggests that pH changes control ASIC gating by protonation/deprotonation of many residues per subunit in different channel domains. Analysis of the function of residues in the palm domain close to the central vertical axis of the channel allowed for prediction of conformational changes of this region during gating. Our study provides a basis for the intrinsic ASIC pH dependence and describes an approach that can also be applied to the investigation of the mechanisms of the pH dependence of other proteins.

QSPR Modelling of Lanthanide‐Organic Complex Stability Constants

The quantitative structure–property relationships (QSPR) have been developed for the stability constants of complexes between 63 different organic ligands and 14 lanthanides. The QSPR models for a series involving a single metal were constructed using only theoretical descriptors for ligands within the CODESSA program. The QSPR models for the series of constants with constant ligand were constructed using various physical properties of metals as descriptors. A good quality of models (47 of the 63 models for ligands gave R 2 higher than 0.90 and only 6 had R 2<0.80 and 10 of the 14 models for metals gave R 2 higher than 0.87 and no model had R 2<0.84) enables reliable prediction of stability constants for any previously unmeasured complex.