Abstract
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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 1787-1801 |
| Number of pages | 15 |
| Journal | Protein Science |
| Volume | 13 |
| Issue number | 7 |
| DOIs | |
| State | Published - Jul 2004 |
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Keywords
- Fold recognition
- Native state ensemble
- Position-specific thermodynamics
- Protein stability
- Protein structure prediction
- Sequential cooperative segments
ASJC Scopus subject areas
- Biochemistry
Cite this
Analysis of the "thermodynamic information content" of a Homo sapiens structural database reveals hierarchical thermodynamic organization. / Larson, Scott A.; Hilser, Vincent J.
In: Protein Science, Vol. 13, No. 7, 07.2004, p. 1787-1801.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Analysis of the "thermodynamic information content" of a Homo sapiens structural database reveals hierarchical thermodynamic organization
AU - Larson, Scott A.
AU - Hilser, Vincent J.
PY - 2004/7
Y1 - 2004/7
N2 - 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.
AB - 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.
KW - Fold recognition
KW - Native state ensemble
KW - Position-specific thermodynamics
KW - Protein stability
KW - Protein structure prediction
KW - Sequential cooperative segments
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UR - http://www.scopus.com/inward/citedby.url?scp=3042572569&partnerID=8YFLogxK
U2 - 10.1110/ps.04706204
DO - 10.1110/ps.04706204
M3 - Article
C2 - 15215522
AN - SCOPUS:3042572569
VL - 13
SP - 1787
EP - 1801
JO - Protein Science
JF - Protein Science
SN - 0961-8368
IS - 7
ER -