Reaction trajectory revealed by a joint analysis of protein data bank.
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 α-thalassemia. This method of meta-analysis provides a general approach to structural dynamics based on static protein structures in this post genomics era.
Center for Advanced Radiation Sources, The University of Chicago, Argonne, Illinois, United States of America ; Renz Research, Inc., Westmont, Illinois, United States of America.
Zhong
Z
Ren
D000818:Animals; D030562:Databases, Protein; D006454:Hemoglobins / Q000235:genetics*; D006801:Humans; D017433:Protein Structure, Secondary; D020539:Sequence Analysis, Protein / Q000379:methods*; D012984:Software; D017085:alpha-Thalassemia / Q000235:genetics*
D006454:Hemoglobins