Analysis of the "thermodynamic information content" of a Homo sapiens structural database reveals hierarchical thermodynamic organization.
Classification of the amounts and types of lower order structural elements in proteins is a prerequisite to effective comparisons between protein folds. In an effort to provide an additional vehicle for fold comparison, we present an alternative classification scheme whereby protein folds are represented in statistical thermodynamic terms in such a way as to illuminate the energetic building blocks within protein structures. The thermodynamic relationship is examined between amino acid sequences and the conformational ensembles for a database of 159 Homo sapiens protein structures ranging from 50 to 250 amino acids. Using hierarchical clustering, it is shown through fold-recognition experiments that (1) eight thermodynamic environmental descriptors sufficiently accounts for the energetic variation within the native state ensembles of the H. sapiens structural database, (2) an amino acid library of only six residue types is sufficient to encode >90% of the thermodynamic information required for fold specificity in the entire database, and (3) structural resolution of the statistically derived environments reveals sequential cooperative segments throughout the protein, which are independent of secondary structure. As the first level of thermodynamic organization in proteins, these segments represent the thermodynamic counterpart to secondary structure.
Larson
Scott A
SA
Department of Human Biological Chemistry and Genetics, 5.162 Medical Research Bldg., University of Texas Medical Branch, Galveston, TX 77555-1068, USA.
Hilser
Vincent J
VJ
D003198:Computer Simulation; D030562:Databases, Protein; D006801:Humans; D011487:Protein Conformation; D017510:Protein Folding; D011506:Proteins / Q000737:chemistry*; D013816:Thermodynamics
D011506:Proteins