From Isotropic to Anisotropic Side Chain Representations: Comparison of Three Models for Residue Contact Estimation

The criterion to determine residue contact is a fundamental problem in deriving knowledge-based mean-force potential energy calculations for protein structures. A frequently used criterion is to require the side chain center-to-center distance or the -to- atom distance to be within a pre-determined cutoff distance. However, the spatially anisotropic nature of the side chain determines that it is challenging to identify the contact pairs. This study compares three side chain contact models: the Atom Distance criteria (ADC) model, the Isotropic Sphere Side chain (ISS) model and the Anisotropic Ellipsoid Side chain (AES) model using 424 high resolution protein structures in the Protein Data Bank. The results indicate that the ADC model is the most accurate and ISS is the worst. The AES model eliminates about 95% of the incorrectly counted contact-pairs in the ISS model. Algorithm analysis shows that AES model is the most computational intensive while ADC model has moderate computational cost. We derived a dataset of the mis-estimated contact pairs by AES model. The most misjudged pairs are Arg-Glu, Arg-Asp and Arg-Tyr. Such a dataset can be useful for developing the improved AES model by incorporating the pair-specific information for the cutoff distance

Oxalate, glycolate, glycerate, sulfate, and citrate

Measurement of oxalate in urine is important for diagnosis of primary hyperoxaluria and the secondary forms resulting from excessive intake or abnormal intestinal absorption of oxalate. Determination of glycolic acid is essential for diagnosis of primary hyperoxaluria type I (PH I), caused by low or absent activity of the liver-specific peroxisomal alanine:glyoxylate aminotransferase. Primary hyperoxaluria type II (PH II) is caused by low or absent activity D-glycerate dehydrogenase and hydroxypyruvate reductase activity, leading to elevated urinary excretion of both oxalate and L-glyceric acid. Ion chromatography HPLC is the method of choice the quantification of oxalate, glycolate, and glycerate and use of urinary filter spots is a practical alternative approach for the collection and safe transport of samples to be analyzed for many metabolic disorders