Protein Engineering, Vol. 16, No. 3, 195-199,
March 2003
© 2003 Oxford University Press
Determination of amino acid pairs sensitive to variants in human ß-glucocerebrosidase by means of a random approach
1 Laboratoire de Toxicocinétique et Pharmacocinétique, Faculté de Pharmacie, Université de la Méditerranée Aix-Marseille II, Marseille, France and 3 Cattedra di Anatomia Patologica, Dipartimento di Ricerche Mediche e Morfologiche, Facoltà di Medicina e Chirurgia, Università degli Studi di Udine, Udine, Italy
2 To whom correspondence should be addressed. E-mail: hongguanglishibahao{at}yahoo.com
In this data-based theoretical analysis, we use the random approach to analyse the amino acid pairs in human ß-glucocerebrosidase in order to determine which amino acid pairs are more sensitive to 109 variants from missense mutant human glucocerebrosidase. The rationale of this study is based on our hypothesis and findings that the harmful variants are more likely to occur at randomly unpredictable amino acid pairs and the unharmful variants are more likely to occur at randomly predictable amino acid pairs. This is because we argue that the randomly predictable amino acid pairs should not be deliberately evolved, whereas the randomly unpredictable amino acid pairs should be deliberately evolved with connection of protein function. The results show, for example, that 93.58% of 109 variants occur at randomly unpredictable amino acid pairs, which account for 71.40% of amino acid pairs in glucocerebrosidase, and the chance of occurrence of the variant is about 4.4 times higher in randomly unpredictable amino acid pairs than in predictable pairs. Hence the randomly unpredictable amino acid pairs are more sensitive to variants in human glucocerebrosidase. The results also suggest that human glucocerebrosidase has a natural tendency to variants.