Statistical and visual morph movie analysis of crystallographic mutant selection bias in protein mutation resource data

Computational Systems Bioinformatics. CSB2003. Proceedings of the 2003 IEEE Bioinformatics Conference. CSB2003 ◽

10.1109/csb.2003.1227317 ◽

2004 ◽

Cited By ~ 1

Author(s):

W.G. Krebs ◽

P.E. Bourne

Keyword(s):

Selection Bias ◽

Mutant Selection ◽

Protein Mutation ◽

Movie Analysis ◽

Resource Data

Download Full-text

STATISTICAL AND VISUAL MORPH MOVIE ANALYSIS OF CRYSTALLOGRAPHIC MUTANT SELECTION BIAS IN PROTEIN MUTATION RESOURCE DATA

Journal of Bioinformatics and Computational Biology ◽

10.1142/s0219720004000478 ◽

2004 ◽

Vol 02 (01) ◽

pp. 61-75 ◽

Cited By ~ 1

Author(s):

WERNER G. KREBS ◽

PHILIP E. BOURNE

Keyword(s):

Amino Acid ◽

Conformational Change ◽

Tertiary Structure ◽

Point Mutations ◽

Data Mining Algorithm ◽

Protein Amino Acid ◽

General Applicability ◽

Mutant Selection ◽

Protein Conformational Change ◽

Resource Data

Structural studies of the effects of non-silent mutations on protein conformational change are an important key in deciphering the language that relates protein amino acid primary structure to tertiary structure. Elsewhere, we presented the Protein Mutant Resource (PMR) database, a set of online tools that systematically identified groups of related mutant structures in the Protein DataBank (PDB), accurately inferred mutant classifications in the Gene Ontology using an innovative, statistically rigorous data-mining algorithm with more general applicability, and illustrated the relationship of these mutant structures via an intuitive user interface. Here, we perform a comprehensive statistical analysis of the effect of PMR mutations on protein tertiary structure. We find that, although the PMR does contain spectacular examples of conformational change, in general there is a counter-intuitive inverse relationship between conformational change (measured as C-alpha displacement or RMS of the core structure) and the number of mutations in a structure. That is, point mutations by structural biologists present in the PDB contrast naturally evolved mutations. We compare the frequency of mutations in the PMR/PDB datasets against the accepted PAM250 natural amino acid mutation frequency to confirm these observations. We generated morph movies from PMR structure pairs using technology previously developed for the Macromolecular Motions Database (), allowing bioinformaticians, geneticists, protein engineers, and rational drug designers to analyze visually the mechanisms of protein conformational change and distinguish between conformational change due to motions (e.g., ligand binding) and mutations. The PMR morph movies and statistics can be freely viewed from the PMR website, .

Download Full-text