Reaction trajectory revealed by a joint analysis of protein data bank.

ABSTRACT: Structural motions along a reaction pathway hold the secret about how a biological macromolecule functions. If each static structure were considered as a snapshot of the protein molecule in action, a large collection of structures would constitute a multidimensional conformational space of an enormous size. Here I present a joint analysis of hundreds of known structures of human hemoglobin in the Protein Data Bank. By applying singular value decomposition to distance matrices of these structures, I demonstrate that this large collection of structural snapshots, derived under a wide range of experimental conditions, arrange orderly along a reaction pathway. The structural motions along this extensive trajectory, including several helical transformations, arrive at a reverse engineered mechanism of the cooperative machinery (Ren, companion article), and shed light on pathological properties of the abnormal homotetrameric hemoglobins from ?-thalassemia. This method of meta-analysis provides a general approach to structural dynamics based on static protein structures in this post genomics era.

SUBMITTER: Ren Z 

PROVIDER: S-EPMC3823880 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature