PubMed · 14826841
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J BADDILEY, E M THAIN, A W RODWELL. 1951-04-07. A possible structure for codecarboxylase.. https://doi.org/10.1038/167556b0
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Amino acid (AA) profiles from body fluids such as blood and urine are clinical indicators for diagnosing metabolic and hepatic diseases. Current quantitative methods, such as liquid chromatography-mass spectrometry (LC-MS) with isotopically labelled internal standards (ISs), are costly and technically demanding. This study proposes a cost-efficient alternative using structural isomers as ISs in a direct liquid infusion (DLI) tandem mass spectrometry (MS/MS) approach. The method leverages chimeric spectra and fragment intensity ratios to quantify AAs, demonstrating high linearity and precision even with a 3D ion trap mass analyser. This approach offers a viable strategy for AA quantification in preventive medicine, particularly for screening metabolic diseases such as phenylketonuria, diabetes, and liver dysfunction.
The concept of amino acid solvent exposure is crucial for understanding and predicting various aspects of protein structure and function. The traditional measures of solvent exposure however suffer from various shortcomings, like for example the inability to distinguish exposed, partly exposed, buried, and deeply buried residues. This article introduces a new measure of solvent exposure called Half-Sphere Exposure that addresses many of the shortcomings of other methods. The new measure outperforms other measures with respect to correlation with protein stability, conservation among fold homologs, amino acid-type dependency and interpretation. The measure consists of the number of Calpha atoms in two half spheres around a residue's Calpha atom. Conceptually, one of the half spheres corresponds to the side chain's neighborhood, the other half sphere being in the opposite direction. We show here that the two half spheres correspond to two regions around an amino acid that are surprisingly distinct in terms of geometry and energy. This aspect of protein structure introduced here forms the basis of the Half-Sphere Exposure measure. The results strongly suggest that in many respects, a 2D measure is inherently much better suited to describe solvent exposure than the traditional 1D measures. Importantly, Half-Sphere Exposure can be calculated from the Calpha atom coordinates only, which abolishes the need for a full-atom model to calculate solvent exposure. Hence, the measure can be used in protein structure prediction methods that are based on various simplified models. Half-Sphere Exposure has great potential for use in protein structure prediction and analysis.
We have analyzed 29 different published matrices of protein pairwise contact potentials (CPs) between amino acids derived from different sets of proteins, either crystallographic structures taken from the Protein Data Bank (PDB) or computer-generated decoys. Each of the CPs is similar to 1 of the 2 matrices derived in the work of Miyazawa and Jernigan (Proteins 1999;34:49-68). The CP matrices of the first class can be approximated with a correlation of order 0.9 by the formula e(ij) = h(i) + h(j), 1 <or= i, j <or= 20, where the residue-type dependent factor h is highly correlated with the frequency of occurrence of a given amino acid type inside proteins. Electrostatic interactions for the potentials of this class are almost negligible. In the potentials belonging to this class, the major contribution to the potentials is the one-body transfer energy of the amino acid from water to the protein environment. Potentials belonging to the second class can be approximated with a correlation of 0.9 by the formula e(ij) = c(0) - h(i)h(j) + q(i)q(j), where c(0) is a constant, h is highly correlated with the Kyte-Doolittle hydrophobicity scale, and a new, less dominant, residue-type dependent factor q is correlated ( approximately 0.9) with amino acid isoelectric points pI. Including electrostatic interactions significantly improves the approximation for this class of potentials. While, the high correlation between potentials of the first class and the hydrophobic transfer energies is well known, the fact that this approximation can work well also for the second class of potentials is a new finding. We interpret potentials of this class as representing energies of contact of amino acid pairs within an average protein environment.