PON-SC – program for identifying steric clashes caused by amino acid substitutions

Amino acid substitutions preserve protein folding by conserving steric and hydrophobicity properties.

We present a comprehensive analysis of amino acid substitution patterns (sets of residues in a position of a multiple alignment) and conservation of physicochemical properties in alignments of protein sequences. Of the one million possible substitution patterns, only a few hundred account for the majority of aligned positions. Very similar distributions of substitution patterns are observed in ...

Classification of Amino Acid Substitutions in Mismatch Repair Proteins Using PON-MMR2.

Variations in mismatch repair (MMR) system genes are causative of Lynch syndrome and other cancers. Thousands of variants have been identified in MMR genes, but the clinical relevance is known for only a small proportion. Recently, the InSiGHT group classified 2,360 MMR variants into five classes. One-third of variants, majority of which is nonsynonymous variants, remain to be of uncertain clin...

Combinatorial codon-based amino acid substitutions.

Twenty Fmoc-protected trinucleotide phosphoramidites representing a complete set of codons for the natural amino acids were chemically synthesized for the first time. A pool of these reagents was incorporated into oligonucleotides at substoichiometric levels to generate two libraries of variants that randomly carry either few or many codon replacements on a region encoding nine amino acids of t...

Amino Acid Substitutions: Effects on Protein Stability

A living cell can be viewed as a biochemical factory, with as many as 100,000 distinct proteins providing the hardware to carry out cellular processes. The roles of these molecular machines include such diverse activities as pumping (e.g. voltage gated membrane channels), motor functions (e.g. flagella), amplification (e.g. cyclic AMP), and catalysis. The ability of a protein to function in one...

Amino Acid Properties and Consequences of Substitutions