title: A new method for quantifying residue conservation and its applications to the protein folding nucleus.
abstract: The conservation of residues in columns of a multiple sequence alignment (MSA) reflects the importance of these residues for maintaining the structure and function of a protein. To date, many scores have been suggested for quantifying residue conservation, but none has achieved the full rigor both in biology and statistics. In this paper, we present a new approach for measuring the evolutionary conservation at aligned positions. Our conservation measure is related to the logarithmic probabilities for aligned positions, and combines the physicochemical properties and the frequencies of amino acids. Such a measure is both biologically and statistically meaningful. For testing the relationship between an amino acid's evolutionary conservation and its role in the Phi-value defined protein folding kinetics, our results indicate that the folding nucleus residues may not be significantly more conserved than other residues by using the biological-relevance weighted statistical scoring method suggested in this paper as an alternative to entropy-based procedures.
authors.affiliation: Institute of Nanoscience, Nanjing University of Aeronautics and Astronautics, Nanjing 210016, China. xsliu@nuaa.edu.cn
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Li
authors.forename: Wanlin
authors.initials: W
authors.lastname: Guo
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
mesh_terms: D000595:Amino Acid Sequence; D019295:Computational Biology / Q000379:methods*; D017124:Conserved Sequence; D019143:Evolution, Molecular; D008432:Mathematical Computing; D017510:Protein Folding