Molecular Biology and Evolution 19:352-356 (2002)
© 2002 Society for Molecular Biology and Evolution
Site-Specific Amino Acid Replacement Matrices from Structurally Constrained Protein Evolution Simulations
Universidad Nacional de Quilmes, Saenz Peña 180, B1876BXD Bernal, Argentina
Evolutionary amino acid replacement rates depend on local structural environment (Overington et al. 1992
; Koshi and Goldstein 1995
). Recent models of protein evolution aim to take such site heterogeneity into account by using site-specific amino acid replacement matrices (Lio and Goldman 1998
; Thorne 2000
). This is a difficult task, mainly because of a lack-of-data problem: too many sequences would be needed to fit the large number of parameters required to specify the replacement matrix for each site. Two strategies have been used to tackle this problem. A first type of model assumes that protein sites can be classified into a limited number of structural classes. Then, class-specific replacement matrices are obtained by analyzing large databases of sequences (Thorne, Goldman, and Jones 1996
; Lio et al. 1998
). These models are promising, provided the assumption of universality of structural classes is a reasonable one. However, such
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