期刊
HUMAN MUTATION
卷 32, 期 10, 页码 1161-1170出版社
WILEY-BLACKWELL
DOI: 10.1002/humu.21555
关键词
SAP annotation; probability; protein stability; disease
资金
- MIUR-FIRB
- LIBI-International Laboratory for Bioinformatics [RBLA039M7M]
- University of Bologna
- Institute of Advanced Studies
Single residue mutations in proteins are known to affect protein stability and function. As a consequence, they can be disease associated. Available computational methods starting from protein sequence/structure can predict whether a mutated residue is or not disease associated and whether it is promoting instability of the protein-folded structure. However, the relationship among stability changes in proteins and their involvement in human diseases still needs to be fully exploited. Here, we try to rationalize in a nutshell the complexity of the question by generalizing over information already stored in public databases. For each single aminoacid polymorphysm (SAP) type, we derive the probability of being disease-related (Pd) and compute from thermodynamic data three indexes indicating the probability of decreasing (P-), increasing (P+), and perturbing the protein structure stability (Pp). Statistically validated analysis of the different P/Pd correlations indicate that Pd best correlates with Pp. Pp/Pd correlation values are as high as 0.49, and increase up to 0.67 when data variability is taken into consideration. This is indicative of a medium/good correlation among Pd and Pp and corroborates the assumption that protein stability changes can also be disease associated at the proteome level. Hum Mutat 32:1161-1170, 2011. (C) 2011 Wiley-Liss, Inc.
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