Inferring property selection pressure from positional residue conservation

In this study, we attempt to understand and explain positional selection pressure in terms of underlying physical and chemical properties. We propose a set of constraining assumptions about how these pressures behave, then describe a procedure for analysing and explaining the distribution of residues at a particular position in a multiple sequence alignment. In contrast to previous approaches, our model takes into account both amino acid frequencies and a large number of physical-chemical properties. By analysing each property separately, it is possible to identify positions where distinct conservation patterns are present. In addition, the model can easily incorporate sequence weights that adjust for bias in the sample sequences. Finally, a test of statistical significance is provided for our conservation measure. The applicability of this method is demonstrated on two HIV-1 proteins: Nef and Env. The tools, data and results presented in this article are available at http://flan.blm.cs.cmu.edu.