Statistical and Visual Morph Movie Analysis of Crystallographic Mutant Selection Bias in Protein Mutation Resource Data

• Authors: Werner G. Krebs;Philip E. Bourne
• Venue: CSB '03 Proceedings of the IEEE Computer Society Conference on Bioinformatics
• Year: 2003

The relationship between protein mutations and conformational change can potentially decipher the languagerelating sequence to structure. Elsewhere, we presentedthe Protein Mutant Resource (PMR), an online tool thatsystematically identified related mutants in the ProteinDataBank (PDB), inferred mutant Gene Ontology classifications using data-mining, and allowed intuitive exploration of relationships between mutant structures. Here,we perform a comprehensive statistical analysis of PMRmutants. Although the PMR contains spectacular conformational changes, generally there is a counter-intuitiveinverse relationship between conformational change andthe number of mutations. That is, PDB mutations contrastnaturally evolved mutations. We compare the frequenciesof mutations in the PMR/PDB datasets against thePAM250 natural mutation frequencies to confirm this. Wemake available morph movies from PMR structure pairs,allowing visual analysis of conformational change andthe ability to distinguish visually between conformationalchange due to motions (e.g.,ligand binding)and mutations. The PMR is at http://pmr.sdsc.edu.