Robustness of the residue conservation score reflecting both frequencies and physicochemistries

Measuring residue conservation at aligned positions has many applications in biology. Recently, a new conservation score has been defined. Unlike the previous methods, the new approach considers both residue frequencies and physicochemistries. Specifically, it measures physicochemistries based on BLOSUM matrices disregarding the meaning of the entries in such matrices, which may involve the problem of log–log probability. In this paper we present a conservation measure that also reflects both frequencies and physicochemistries while considering the fact that the entries of BLOSUM matrices are already interpreted as log probability. When the supposed score is applied to 14 protein examples, the results show that these two conservation scores are equivalent aside from the different score ranges. The method is also used to score the functional sites of three protein families. Compared with the widely used entropy-based methods, the resulting scores are more robust and consistent in the sense that the functional sites are much more conserved because of functional constraints.