Predicting the functional consequence of a given amino acid replacement, that is, the difference between the wild type protein and its nonsynony-mous single nucleotide polymorph variants (nsSNPs) is a great challenge. This is especially true in the case of large membrane proteins, like ABC transporters. Kelly et al. has published such an ambitious study in a recent issue of Protein Science focusing on nsSNP in structurally conserved segments within the nucleotide binding domains (NBDs) of ABC transporters supposed to be involved in interdomain communication. With the aid of structural rationalization the authors predicted the impact of 40 nsSNPs found in seven clinically important human ABC transporters using a bivalent scoring: disease or neutral.
展开▼
