Preprints available on bioRxiv
141.
Bowers, P M; Strauss, C E; Baker, David
De novo protein structure determination using sparse NMR data. Journal Article
In: Journal of biomolecular NMR, vol. 18, pp. 311-8, 2000, ISSN: 0925-2738.
@article{193,
title = {De novo protein structure determination using sparse NMR data.},
author = { P M Bowers and C E Strauss and David Baker},
issn = {0925-2738},
year = {2000},
date = {2000-12-01},
journal = {Journal of biomolecular NMR},
volume = {18},
pages = {311-8},
abstract = {We describe a method for generating moderate to high-resolution protein structures using limited NMR data combined with the ab initio protein structure prediction method Rosetta. Peptide fragments are selected from proteins of known structure based on sequence similarity and consistency with chemical shift and NOE data. Models are built from these fragments by minimizing an energy function that favors hydrophobic burial, strand pairing, and satisfaction of NOE constraints. Models generated using this procedure with approximately 1 NOE constraint per residue are in some cases closer to the corresponding X-ray structures than the published NMR solution structures. The method requires only the sparse constraints available during initial stages of NMR structure determination, and thus holds promise for increasing the speed with which protein solution structures can be determined.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe a method for generating moderate to high-resolution protein structures using limited NMR data combined with the ab initio protein structure prediction method Rosetta. Peptide fragments are selected from proteins of known structure based on sequence similarity and consistency with chemical shift and NOE data. Models are built from these fragments by minimizing an energy function that favors hydrophobic burial, strand pairing, and satisfaction of NOE constraints. Models generated using this procedure with approximately 1 NOE constraint per residue are in some cases closer to the corresponding X-ray structures than the published NMR solution structures. The method requires only the sparse constraints available during initial stages of NMR structure determination, and thus holds promise for increasing the speed with which protein solution structures can be determined.
142.
Bystroff, C; Thorsson, V; Baker, David
HMMSTR: a hidden Markov model for local sequence-structure correlations in proteins Journal Article
In: Journal of molecular biology, vol. 301, pp. 173-90, 2000, ISSN: 0022-2836.
@article{194,
title = {HMMSTR: a hidden Markov model for local sequence-structure correlations in proteins},
author = { C Bystroff and V Thorsson and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/bystroff00A.pdf},
issn = {0022-2836},
year = {2000},
date = {2000-08-01},
journal = {Journal of molecular biology},
volume = {301},
pages = {173-90},
abstract = {We describe a hidden Markov model, HMMSTR, for general protein sequence based on the I-sites library of sequence-structure motifs. Unlike the linear hidden Markov models used to model individual protein families, HMMSTR has a highly branched topology and captures recurrent local features of protein sequences and structures that transcend protein family boundaries. The model extends the I-sites library by describing the adjacencies of different sequence-structure motifs as observed in the protein database and, by representing overlapping motifs in a much more compact form, achieves a great reduction in parameters. The HMM attributes a considerably higher probability to coding sequence than does an equivalent dipeptide model, predicts secondary structure with an accuracy of 74.3 %, backbone torsion angles better than any previously reported method and the structural context of beta strands and turns with an accuracy that should be useful for tertiary structure prediction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe a hidden Markov model, HMMSTR, for general protein sequence based on the I-sites library of sequence-structure motifs. Unlike the linear hidden Markov models used to model individual protein families, HMMSTR has a highly branched topology and captures recurrent local features of protein sequences and structures that transcend protein family boundaries. The model extends the I-sites library by describing the adjacencies of different sequence-structure motifs as observed in the protein database and, by representing overlapping motifs in a much more compact form, achieves a great reduction in parameters. The HMM attributes a considerably higher probability to coding sequence than does an equivalent dipeptide model, predicts secondary structure with an accuracy of 74.3 %, backbone torsion angles better than any previously reported method and the structural context of beta strands and turns with an accuracy that should be useful for tertiary structure prediction.
143.
Baker, David
A surprising simplicity to protein folding Journal Article
In: Nature, vol. 405, pp. 39-42, 2000, ISSN: 0028-0836.
@article{192,
title = {A surprising simplicity to protein folding},
author = { David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/baker00A.pdf},
issn = {0028-0836},
year = {2000},
date = {2000-05-01},
journal = {Nature},
volume = {405},
pages = {39-42},
abstract = {The polypeptide chains that make up proteins have thousands of atoms and hence millions of possible inter-atomic interactions. It might be supposed that the resulting complexity would make prediction of protein structure and protein-folding mechanisms nearly impossible. But the fundamental physics underlying folding may be much simpler than this complexity would lead us to expect folding rates and mechanisms appear to be largely determined by the topology of the native (folded) state, and new methods have shown great promise in predicting protein-folding mechanisms and the three-dimensional structures of proteins.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The polypeptide chains that make up proteins have thousands of atoms and hence millions of possible inter-atomic interactions. It might be supposed that the resulting complexity would make prediction of protein structure and protein-folding mechanisms nearly impossible. But the fundamental physics underlying folding may be much simpler than this complexity would lead us to expect folding rates and mechanisms appear to be largely determined by the topology of the native (folded) state, and new methods have shown great promise in predicting protein-folding mechanisms and the three-dimensional structures of proteins.
144.
Plaxco, K W; Larson, S; Ruczinski, I; Riddle, D S; Thayer, E C; Buchwitz, B; Davidson, A R; Baker, David
Evolutionary conservation in protein folding kinetics Journal Article
In: Journal of molecular biology, vol. 298, pp. 303-12, 2000, ISSN: 0022-2836.
@article{200,
title = {Evolutionary conservation in protein folding kinetics},
author = { K W Plaxco and S Larson and I Ruczinski and D S Riddle and E C Thayer and B Buchwitz and A R Davidson and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/plaxco00a.pdf},
issn = {0022-2836},
year = {2000},
date = {2000-04-01},
journal = {Journal of molecular biology},
volume = {298},
pages = {303-12},
abstract = {The sequence and structural conservation of folding transition states have been predicted on theoretical grounds. Using homologous sequence alignments of proteins previously characterized via coupled mutagenesis/kinetics studies, we tested these predictions experimentally. Only one of the six appropriately characterized proteins exhibits a statistically significant correlation between residuestextquoteright roles in transition state structure and their evolutionary conservation. However, a significant correlation is observed between the contributions of individual sequence positions to the transition state structure across a set of homologous proteins. Thus the structure of the folding transition state ensemble appears to be more highly conserved than the specific interactions that stabilize it.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The sequence and structural conservation of folding transition states have been predicted on theoretical grounds. Using homologous sequence alignments of proteins previously characterized via coupled mutagenesis/kinetics studies, we tested these predictions experimentally. Only one of the six appropriately characterized proteins exhibits a statistically significant correlation between residuestextquoteright roles in transition state structure and their evolutionary conservation. However, a significant correlation is observed between the contributions of individual sequence positions to the transition state structure across a set of homologous proteins. Thus the structure of the folding transition state ensemble appears to be more highly conserved than the specific interactions that stabilize it.
145.
Alm, E; Baker, David
Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 96, pp. 11305-10, 1999, ISSN: 0027-8424.
@article{48,
title = {Prediction of protein-folding mechanisms from free-energy landscapes derived from native structures},
author = { E Alm and David Baker},
issn = {0027-8424},
year = {1999},
date = {1999-09-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {96},
pages = {11305-10},
abstract = {Guided by recent experimental results suggesting that protein-folding rates and mechanisms are determined largely by native-state topology, we develop a simple model for protein folding free-energy landscapes based on native-state structures. The configurations considered by the model contain one or two contiguous stretches of residues ordered as in the native structure with all other residues completely disordered; the free energy of each configuration is the difference between the entropic cost of ordering the residues, which depends on the total number of residues ordered and the length of the loop between the two ordered segments, and the favorable attractive interactions, which are taken to be proportional to the total surface area buried by the ordered residues in the native structure. Folding kinetics are modeled by allowing only one residue to become ordered/disordered at a time, and a rigorous and exact method is used to identify free-energy maxima on the lowest free-energy paths connecting the fully disordered and fully ordered configurations. The distribution of structure in these free-energy maxima, which comprise the transition-state ensemble in the model, are reasonably consistent with experimental data on the folding transition state for five of seven proteins studied. Thus, the model appears to capture, at least in part, the basic physics underlying protein folding and the aspects of native-state topology that determine protein-folding mechanisms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Guided by recent experimental results suggesting that protein-folding rates and mechanisms are determined largely by native-state topology, we develop a simple model for protein folding free-energy landscapes based on native-state structures. The configurations considered by the model contain one or two contiguous stretches of residues ordered as in the native structure with all other residues completely disordered; the free energy of each configuration is the difference between the entropic cost of ordering the residues, which depends on the total number of residues ordered and the length of the loop between the two ordered segments, and the favorable attractive interactions, which are taken to be proportional to the total surface area buried by the ordered residues in the native structure. Folding kinetics are modeled by allowing only one residue to become ordered/disordered at a time, and a rigorous and exact method is used to identify free-energy maxima on the lowest free-energy paths connecting the fully disordered and fully ordered configurations. The distribution of structure in these free-energy maxima, which comprise the transition-state ensemble in the model, are reasonably consistent with experimental data on the folding transition state for five of seven proteins studied. Thus, the model appears to capture, at least in part, the basic physics underlying protein folding and the aspects of native-state topology that determine protein-folding mechanisms.
146.
Simons, K T; Ruczinski, I; Kooperberg, C; Fox, B A; Bystroff, C; Baker, D
Improved recognition of native-like protein structures using a combination of sequence-dependent and sequence-independent features of proteins Journal Article
In: Proteins, vol. 34, pp. 82-95, 1999, ISSN: 0887-3585.
@article{322,
title = {Improved recognition of native-like protein structures using a combination of sequence-dependent and sequence-independent features of proteins},
author = { K T Simons and I Ruczinski and C Kooperberg and B A Fox and C Bystroff and D Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/simons98A.pdf},
issn = {0887-3585},
year = {1999},
date = {1999-01-01},
journal = {Proteins},
volume = {34},
pages = {82-95},
abstract = {We describe the development of a scoring function based on the decomposition P(structure/sequence) proportional to P(sequence/structure) *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 beta-strands into beta-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 approximately 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.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe the development of a scoring function based on the decomposition P(structure/sequence) proportional to P(sequence/structure) *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 beta-strands into beta-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 approximately 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.
147.
Simons, K T; Bonneau, R; Ruczinski, I; Baker, David
Ab initio protein structure prediction of CASP III targets using ROSETTA Journal Article
In: Proteins, vol. Suppl 3, pp. 171-6, 1999, ISSN: 0887-3585.
@article{41,
title = {Ab initio protein structure prediction of CASP III targets using ROSETTA},
author = { K T Simons and R Bonneau and I Ruczinski and David Baker},
issn = {0887-3585},
year = {1999},
date = {1999-00-01},
journal = {Proteins},
volume = {Suppl 3},
pages = {171-6},
abstract = {To generate structures consistent with both the local and nonlocal interactions responsible for protein stability, 3 and 9 residue fragments of known structures with local sequences similar to the target sequence were assembled into complete tertiary structures using a Monte Carlo simulated annealing procedure (Simons et al., J Mol Biol 1997; 268:209-225). The scoring function used in the simulated annealing procedure consists of sequence-dependent terms representing hydrophobic burial and specific pair interactions such as electrostatics and disulfide bonding and sequence-independent terms representing hard sphere packing, alpha-helix and beta-strand packing, and the collection of beta-strands in beta-sheets (Simons et al., Proteins 1999;34:82-95). For each of 21 small, ab initio targets, 1,200 final structures were constructed, each the result of 100,000 attempted fragment substitutions. The five structures submitted for the CASP III experiment were chosen from the approximately 25 structures with the lowest scores in the broadest minima (assessed through the number of structural neighbors; Shortle et al., Proc Natl Acad Sci USA 1998;95:1158-1162). The results were encouraging: highlights of the predictions include a 99-residue segment for MarA with an rmsd of 6.4 A to the native structure, a 95-residue (full length) prediction for the EH2 domain of EPS15 with an rmsd of 6.0 A, a 75-residue segment of DNAB helicase with an rmsd of 4.7 A, and a 67-residue segment of ribosomal protein L30 with an rmsd of 3.8 A. These results suggest that ab initio methods may soon become useful for low-resolution structure prediction for proteins that lack a close homologue of known structure.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To generate structures consistent with both the local and nonlocal interactions responsible for protein stability, 3 and 9 residue fragments of known structures with local sequences similar to the target sequence were assembled into complete tertiary structures using a Monte Carlo simulated annealing procedure (Simons et al., J Mol Biol 1997; 268:209-225). The scoring function used in the simulated annealing procedure consists of sequence-dependent terms representing hydrophobic burial and specific pair interactions such as electrostatics and disulfide bonding and sequence-independent terms representing hard sphere packing, alpha-helix and beta-strand packing, and the collection of beta-strands in beta-sheets (Simons et al., Proteins 1999;34:82-95). For each of 21 small, ab initio targets, 1,200 final structures were constructed, each the result of 100,000 attempted fragment substitutions. The five structures submitted for the CASP III experiment were chosen from the approximately 25 structures with the lowest scores in the broadest minima (assessed through the number of structural neighbors; Shortle et al., Proc Natl Acad Sci USA 1998;95:1158-1162). The results were encouraging: highlights of the predictions include a 99-residue segment for MarA with an rmsd of 6.4 A to the native structure, a 95-residue (full length) prediction for the EH2 domain of EPS15 with an rmsd of 6.0 A, a 75-residue segment of DNAB helicase with an rmsd of 4.7 A, and a 67-residue segment of ribosomal protein L30 with an rmsd of 3.8 A. These results suggest that ab initio methods may soon become useful for low-resolution structure prediction for proteins that lack a close homologue of known structure.
148.
Kim, David E; Yi, Q; Gladwin, S T; Goldberg, J M; Baker, David
The single helix in protein L is largely disrupted at the rate-limiting step in folding Journal Article
In: Journal of molecular biology, vol. 284, pp. 807-15, 1998, ISSN: 0022-2836.
@article{209,
title = {The single helix in protein L is largely disrupted at the rate-limiting step in folding},
author = { David E Kim and Q Yi and S T Gladwin and J M Goldberg and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/kim98A_0.pdf},
issn = {0022-2836},
year = {1998},
date = {1998-12-01},
journal = {Journal of molecular biology},
volume = {284},
pages = {807-15},
abstract = {To investigate the role of helix formation in the folding of protein L, a 62 residue alpha/beta protein, we studied the consequences of both single and multiple mutations in the helix on the kinetics of folding. A triple mutant with 11 additional carbon atoms in core residues in the amino-terminal portion of the helix folded substantially faster than wild type, suggesting that hydrophobic association with residues elsewhere in the protein occurs at the rate-limiting step in folding. However, helix-destabilizing mutations had little effect on the rate of folding; in particular, a triple glycine substitution on the solvent-exposed side of the helix increased the unfolding rate 56-fold while reducing the folding rate less than threefold. Thus, in contrast to the predictions of models of folding involving the coalescence of well-formed secondary structure elements, the single helix in protein L appears to be largely disrupted at the rate-limiting step in folding and unfolding.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
To investigate the role of helix formation in the folding of protein L, a 62 residue alpha/beta protein, we studied the consequences of both single and multiple mutations in the helix on the kinetics of folding. A triple mutant with 11 additional carbon atoms in core residues in the amino-terminal portion of the helix folded substantially faster than wild type, suggesting that hydrophobic association with residues elsewhere in the protein occurs at the rate-limiting step in folding. However, helix-destabilizing mutations had little effect on the rate of folding; in particular, a triple glycine substitution on the solvent-exposed side of the helix increased the unfolding rate 56-fold while reducing the folding rate less than threefold. Thus, in contrast to the predictions of models of folding involving the coalescence of well-formed secondary structure elements, the single helix in protein L appears to be largely disrupted at the rate-limiting step in folding and unfolding.
149.
Shortle, D; Simons, K T; Baker, David
Clustering of low-energy conformations near the native structures of small proteins Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 95, pp. 11158-62, 1998, ISSN: 0027-8424.
@article{213,
title = {Clustering of low-energy conformations near the native structures of small proteins},
author = { D Shortle and K T Simons and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/shortle98A.pdf},
issn = {0027-8424},
year = {1998},
date = {1998-09-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {95},
pages = {11158-62},
abstract = {Recent experimental studies of the denatured state and theoretical analyses of the folding landscape suggest that there are a large multiplicity of low-energy, partially folded conformations near the native state. In this report, we describe a strategy for predicting protein structure based on the working hypothesis that there are a greater number of low-energy conformations surrounding the correct fold than there are surrounding low-energy incorrect folds. To test this idea, 12 ensembles of 500 to 1,000 low-energy structures for 10 small proteins were analyzed by calculating the rms deviation of the Calpha coordinates between each conformation and every other conformation in the ensemble. In all 12 cases, the conformation with the greatest number of conformations within 4-A rms deviation was closer to the native structure than were the majority of conformations in the ensemble, and in most cases it was among the closest 1 to 5%. These results suggest that, to fold efficiently and retain robustness to changes in amino acid sequence, proteins may have evolved a native structure situated within a broad basin of low-energy conformations, a feature which could facilitate the prediction of protein structure at low resolution.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Recent experimental studies of the denatured state and theoretical analyses of the folding landscape suggest that there are a large multiplicity of low-energy, partially folded conformations near the native state. In this report, we describe a strategy for predicting protein structure based on the working hypothesis that there are a greater number of low-energy conformations surrounding the correct fold than there are surrounding low-energy incorrect folds. To test this idea, 12 ensembles of 500 to 1,000 low-energy structures for 10 small proteins were analyzed by calculating the rms deviation of the Calpha coordinates between each conformation and every other conformation in the ensemble. In all 12 cases, the conformation with the greatest number of conformations within 4-A rms deviation was closer to the native structure than were the majority of conformations in the ensemble, and in most cases it was among the closest 1 to 5%. These results suggest that, to fold efficiently and retain robustness to changes in amino acid sequence, proteins may have evolved a native structure situated within a broad basin of low-energy conformations, a feature which could facilitate the prediction of protein structure at low resolution.
150.
Bystroff, C; Baker, D
Prediction of local structure in proteins using a library of sequence-structure motifs Journal Article
In: Journal of molecular biology, vol. 281, pp. 565-77, 1998, ISSN: 0022-2836.
@article{311,
title = {Prediction of local structure in proteins using a library of sequence-structure motifs},
author = { C Bystroff and D Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/bystroff98A.pdf},
issn = {0022-2836},
year = {1998},
date = {1998-08-01},
journal = {Journal of molecular biology},
volume = {281},
pages = {565-77},
abstract = {We describe a new method for local protein structure prediction based on a library of short sequence pattern that correlate strongly with protein three-dimensional structural elements. The library was generated using an automated method for finding correlations between protein sequence and local structure, and contains most previously described local sequence-structure correlations as well as new relationships, including a diverging type-II beta-turn, a frayed helix, and a proline-terminated helix. The query sequence is scanned for segments 7 to 19 residues in length that strongly match one of the 82 patterns in the library. Matching segments are assigned the three-dimensional structure characteristic of the corresponding sequence pattern, and backbone torsion angles for the entire query sequence are then predicted by piecing together mutually compatible segment predictions. In predictions of local structure in a test set of 55 proteins, about 50% of all residues, and 76% of residues covered by high-confidence predictions, were found in eight-residue segments within 1.4 A of their true structures. The predictions are complementary to traditional secondary structure predictions because they are considerably more specific in turn regions, and may contribute to ab initio tertiary structure prediction and fold recognition.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe a new method for local protein structure prediction based on a library of short sequence pattern that correlate strongly with protein three-dimensional structural elements. The library was generated using an automated method for finding correlations between protein sequence and local structure, and contains most previously described local sequence-structure correlations as well as new relationships, including a diverging type-II beta-turn, a frayed helix, and a proline-terminated helix. The query sequence is scanned for segments 7 to 19 residues in length that strongly match one of the 82 patterns in the library. Matching segments are assigned the three-dimensional structure characteristic of the corresponding sequence pattern, and backbone torsion angles for the entire query sequence are then predicted by piecing together mutually compatible segment predictions. In predictions of local structure in a test set of 55 proteins, about 50% of all residues, and 76% of residues covered by high-confidence predictions, were found in eight-residue segments within 1.4 A of their true structures. The predictions are complementary to traditional secondary structure predictions because they are considerably more specific in turn regions, and may contribute to ab initio tertiary structure prediction and fold recognition.
151.
Yi, Q; Bystroff, C; Rajagopal, P; Klevit, R E; Baker, David
Prediction and structural characterization of an independently folding substructure in the src SH3 domain Journal Article
In: Journal of molecular biology, vol. 283, pp. 293-300, 1998, ISSN: 0022-2836.
@article{212,
title = {Prediction and structural characterization of an independently folding substructure in the src SH3 domain},
author = { Q Yi and C Bystroff and P Rajagopal and R E Klevit and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/yi98A.pdf},
issn = {0022-2836},
year = {1998},
date = {1998-00-01},
journal = {Journal of molecular biology},
volume = {283},
pages = {293-300},
abstract = {Previous studies of the conformations of peptides spanning the length of the alpha-spectrin SH3 domain suggested that SH3 domains lack independently folding substructures. Using a local structure prediction method based on the I-sites library of sequence-structure motifs, we identified a seven residue peptide in the src SH3 domain predicted to adopt a native-like structure, a type II beta-turn bridging unpaired beta-strands, that was not contained intact in any of the SH3 domain peptides studied earlier. NMR characterization confirmed that the isolated peptide, FKKGERL, adopts a structure similar to that adopted in the native protein: the NOE and 3JNHalpha coupling constant patterns were indicative of a type II beta-turn, and NOEs between the Phe and the Leu side-chains suggest that they are juxtaposed as in the prediction and the native structure. These results support the idea that high-confidence I-sites predictions identify protein segments that are likely to form native-like structures early in folding.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Previous studies of the conformations of peptides spanning the length of the alpha-spectrin SH3 domain suggested that SH3 domains lack independently folding substructures. Using a local structure prediction method based on the I-sites library of sequence-structure motifs, we identified a seven residue peptide in the src SH3 domain predicted to adopt a native-like structure, a type II beta-turn bridging unpaired beta-strands, that was not contained intact in any of the SH3 domain peptides studied earlier. NMR characterization confirmed that the isolated peptide, FKKGERL, adopts a structure similar to that adopted in the native protein: the NOE and 3JNHalpha coupling constant patterns were indicative of a type II beta-turn, and NOEs between the Phe and the Leu side-chains suggest that they are juxtaposed as in the prediction and the native structure. These results support the idea that high-confidence I-sites predictions identify protein segments that are likely to form native-like structures early in folding.
152.
Bystroff, C; Baker, David
Blind predictions of local protein structure in CASP2 targets using the I-sites library Journal Article
In: Proteins, vol. Suppl 1, pp. 167-71, 1997, ISSN: 0887-3585.
@article{30,
title = {Blind predictions of local protein structure in CASP2 targets using the I-sites library},
author = { C Bystroff and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/bystroff97A.pdf},
issn = {0887-3585},
year = {1997},
date = {1997-00-01},
journal = {Proteins},
volume = {Suppl 1},
pages = {167-71},
abstract = {Blind predictions of the local structure of nine CASP2 targets were made using the I-sites library of short sequence--structure motifs, revealing strengths and weaknesses in this new knowledge-based method. Many turns between secondary structural elements were accurately predicted. Estimates of the confidence of prediction correlated well with the accuracy over the whole set. Bias toward structures used to develop the library was minimal, probably because of the extensive use of cross-validation. However, helix positions were better predicted by the PHD program. The method is likely to be sensitive to the quality of the sequence alignment. A general measure for evaluating local structure predictions is suggested.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Blind predictions of the local structure of nine CASP2 targets were made using the I-sites library of short sequence–structure motifs, revealing strengths and weaknesses in this new knowledge-based method. Many turns between secondary structural elements were accurately predicted. Estimates of the confidence of prediction correlated well with the accuracy over the whole set. Bias toward structures used to develop the library was minimal, probably because of the extensive use of cross-validation. However, helix positions were better predicted by the PHD program. The method is likely to be sensitive to the quality of the sequence alignment. A general measure for evaluating local structure predictions is suggested.
153.
Han, K F; Baker, David
Global properties of the mapping between local amino acid sequence and local structure in proteins Journal Article
In: Proceedings of the National Academy of Sciences of the United States of America, vol. 93, pp. 5814-8, 1996, ISSN: 0027-8424.
@article{215,
title = {Global properties of the mapping between local amino acid sequence and local structure in proteins},
author = { K F Han and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/han96A.pdf},
issn = {0027-8424},
year = {1996},
date = {1996-06-01},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
volume = {93},
pages = {5814-8},
abstract = {Local protein structure prediction efforts have consistently failed to exceed approximately 70% accuracy. We characterize the degeneracy of the mapping from local sequence to local structure responsible for this failure by investigating the extent to which similar sequence segments found in different proteins adopt similar three-dimensional structures. Sequence segments 3-15 residues in length from 154 different protein families are partitioned into neighborhoods containing segments with similar sequences using cluster analysis. The consistency of the sequence-to-structure mapping is assessed by comparing the local structures adopted by sequence segments in the same neighborhood in proteins of known structure. In the 154 families, 45% and 28% of the positions occur in neighborhoods in which one and two local structures predominate, respectively. The sequence patterns that characterize the neighborhoods in the first class probably include virtually all of the short sequence motifs in proteins that consistently occur in a particular local structure. These patterns, many of which occur in transitions between secondary structural elements, are an interesting combination of previously studied and novel motifs. The identification of sequence patterns that consistently occur in one or a small number of local structures in proteins should contribute to the prediction of protein structure from sequence.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Local protein structure prediction efforts have consistently failed to exceed approximately 70% accuracy. We characterize the degeneracy of the mapping from local sequence to local structure responsible for this failure by investigating the extent to which similar sequence segments found in different proteins adopt similar three-dimensional structures. Sequence segments 3-15 residues in length from 154 different protein families are partitioned into neighborhoods containing segments with similar sequences using cluster analysis. The consistency of the sequence-to-structure mapping is assessed by comparing the local structures adopted by sequence segments in the same neighborhood in proteins of known structure. In the 154 families, 45% and 28% of the positions occur in neighborhoods in which one and two local structures predominate, respectively. The sequence patterns that characterize the neighborhoods in the first class probably include virtually all of the short sequence motifs in proteins that consistently occur in a particular local structure. These patterns, many of which occur in transitions between secondary structural elements, are an interesting combination of previously studied and novel motifs. The identification of sequence patterns that consistently occur in one or a small number of local structures in proteins should contribute to the prediction of protein structure from sequence.
154.
Han, K F; Baker, David
Recurring local sequence motifs in proteins Journal Article
In: Journal of molecular biology, vol. 251, pp. 176-87, 1995, ISSN: 0022-2836.
@article{22,
title = {Recurring local sequence motifs in proteins},
author = { K F Han and David Baker},
url = {https://www.bakerlab.org/wp-content/uploads/2016/06/han95A.pdf},
issn = {0022-2836},
year = {1995},
date = {1995-08-01},
journal = {Journal of molecular biology},
volume = {251},
pages = {176-87},
abstract = {We describe a completely automated approach to identifying local sequence motifs that transcend protein family boundaries. Cluster analysis is used to identify recurring patterns of variation at single positions and in short segments of contiguous positions in multiple sequence alignments for a non-redundant set of protein families. Parallel experiments on simulated data sets constructed with the overall residue frequencies of proteins but not the inter-residue correlations show that naturally occurring protein sequences are significantly more clustered than the corresponding random sequences for window lengths ranging from one to 13 contiguous positions. The patterns of variation at single positions are not in general surprising: chemically similar amino acids tend to be grouped together. More interesting patterns emerge as the window length increases. The patterns of variation for longer window lengths are in part recognizable patterns of hydrophobic and hydrophilic residues, and in part less obvious combinations. A particularly interesting class of patterns features highly conserved glycine residues. The patterns provide a means to abstract the information contained in multiple sequence alignments and may be useful for comparison of distantly related sequences or sequence families and for protein structure prediction.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We describe a completely automated approach to identifying local sequence motifs that transcend protein family boundaries. Cluster analysis is used to identify recurring patterns of variation at single positions and in short segments of contiguous positions in multiple sequence alignments for a non-redundant set of protein families. Parallel experiments on simulated data sets constructed with the overall residue frequencies of proteins but not the inter-residue correlations show that naturally occurring protein sequences are significantly more clustered than the corresponding random sequences for window lengths ranging from one to 13 contiguous positions. The patterns of variation at single positions are not in general surprising: chemically similar amino acids tend to be grouped together. More interesting patterns emerge as the window length increases. The patterns of variation for longer window lengths are in part recognizable patterns of hydrophobic and hydrophilic residues, and in part less obvious combinations. A particularly interesting class of patterns features highly conserved glycine residues. The patterns provide a means to abstract the information contained in multiple sequence alignments and may be useful for comparison of distantly related sequences or sequence families and for protein structure prediction.
2026
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2025
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2024
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2023
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2022
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2021
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2020
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2019
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2018
FROM THE LAB
Sorry, no publications matched your criteria.
COLLABORATOR LED
Sorry, no publications matched your criteria.
2017-1988
ALL PAPERS
Sorry, no publications matched your criteria.