TY - JOUR
T1 - Improved recognition of native-like protein structures using a combination of sequence-dependent and sequence-independent features of proteins
AU - Simons, Kim T.
AU - Ruczinski, Ingo
AU - Kooperberg, Charles
AU - Fox, Brian A.
AU - Bystroff, Chris
AU - Baker, David
PY - 1999/1/1
Y1 - 1999/1/1
N2 - We describe the development of a scoring function based on the decomposition P(structure/sequence) ∞ P(sequence/structure) α P(structure), which outperforms previous scoring functions in correctly identifying native- like protein structures in large ensembles of compact decoys. The first term captures sequence-dependent features of protein structures, such as the burial of hydrophobic residues in the core, the second term, universal sequence-independent features, such as the assembly of β-strands into β- sheets. The efficacies of a wide variety of sequence-dependent and sequence- independent features of protein structures for recognizing native-like structures were systematically evaluated using ensembles of ~30,000 compact conformations with fixed secondary structure for each of 17 small protein domains. The best results were obtained using a core scoring function with P(sequence/structure) parameterized similarly to our previous work (Simons et al., J Mol Biol 1997;268:209-225] and P(structure) focused on secondary structure packing preferences; while several additional features had some discriminatory power on their own, they did not provide any additional discriminatory power when combined with the core scoring function. Our results, on both the training set and the independent decoy set of Park and Levitt (J Mol Biol 1996;258:367-392), suggest that this scoring function should contribute to the prediction of tertiary structure from knowledge of sequence and secondary structure.
AB - We describe the development of a scoring function based on the decomposition P(structure/sequence) ∞ P(sequence/structure) α P(structure), which outperforms previous scoring functions in correctly identifying native- like protein structures in large ensembles of compact decoys. The first term captures sequence-dependent features of protein structures, such as the burial of hydrophobic residues in the core, the second term, universal sequence-independent features, such as the assembly of β-strands into β- sheets. The efficacies of a wide variety of sequence-dependent and sequence- independent features of protein structures for recognizing native-like structures were systematically evaluated using ensembles of ~30,000 compact conformations with fixed secondary structure for each of 17 small protein domains. The best results were obtained using a core scoring function with P(sequence/structure) parameterized similarly to our previous work (Simons et al., J Mol Biol 1997;268:209-225] and P(structure) focused on secondary structure packing preferences; while several additional features had some discriminatory power on their own, they did not provide any additional discriminatory power when combined with the core scoring function. Our results, on both the training set and the independent decoy set of Park and Levitt (J Mol Biol 1996;258:367-392), suggest that this scoring function should contribute to the prediction of tertiary structure from knowledge of sequence and secondary structure.
KW - Fold recognition
KW - Knowledge-based scoring functions
KW - Protein folding
KW - Structure prediction
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U2 - 10.1002/(SICI)1097-0134(19990101)34:1<82::AID-PROT7>3.0.CO;2-A
DO - 10.1002/(SICI)1097-0134(19990101)34:1<82::AID-PROT7>3.0.CO;2-A
M3 - Article
C2 - 10336385
AN - SCOPUS:0032929780
SN - 0887-3585
VL - 34
SP - 82
EP - 95
JO - Proteins: Structure, Function and Genetics
JF - Proteins: Structure, Function and Genetics
IS - 1
ER -