A Family of Evolution–Entropy Hybrid Methods for Ranking Protein Residues by Importance

Mihalek, Ivana; Reš, I.; Lichtarge, Olivier

doi:10.1016/j.jmb.2003.12.078

Cited by 281 publications

(328 citation statements)

References 35 publications

Supporting

Mentioning

319

Contrasting

Unclassified

Order By: Relevance

“…Mihalek, et al discuss a comparative study of the ability of these methods to predict important residues. 28 The integer value ET rank 27 (ivET) for the residue position i in the query protein can be expressed…”

Section: Residue Ranking Methodsmentioning

confidence: 99%

“…Real value ET (rvET) method 28 ranks the evolutionary importance of residues in a protein family, which is based on the column variation in multiple sequence alignments and evolutionary information extracted from the phylogenetic tree. Shannon Entropy is calculated for the entire alignment, and then recalculated for all the subgroups of the alignment selected by the phylogenetic tree.…”

Section: Residue Ranking Methodsmentioning

confidence: 99%

“…Different ranking methods were used each time to control for method-specific bias: the integer value ET 27 (ivET), Shannon Entropy 51 and the current standard real value ET 28 (rvET), which is resilient to errors like entropy, but exploits the phylogenetic information like ivET. Each method is reviewed in ''Materials and Methods'' section.…”

Section: Correlations With Deleterious Sequence Perturbationsmentioning

confidence: 99%

“…[16][17][18][19] Here, we focus on comparative, or evolutionary approaches, [20][21][22][23][24][25][26] and specifically on the evolutionary trace (ET). 27,28 ET maps functional hotspots on protein structures: areas of the protein where amino acids that impact function concentrate. In large-scale analyses, ET ranked amino acids by evolutionary importance 8,29 such that the top-ranked ones formed structural clusters [30][31][32] that overlapped and predicted functional sites.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation

et al. 2010

Self Cite

View full text Add to dashboard Cite

Protein functional sites control most biological processes and are important targets for drug design and protein engineering. To characterize them, the evolutionary trace (ET) ranks the relative importance of residues according to their evolutionary variations. Generally, top-ranked residues cluster spatially to define evolutionary hotspots that predict functional sites in structures. Here, various functions that measure the physical continuity of ET ranks among neighboring residues in the structure, or in the sequence, are shown to inform sequence selection and to improve functional site resolution. This is shown first, in 110 proteins, for which the overlap between top-ranked residues and actual functional sites rose by 8% in significance. Then, on a structural proteomic scale, optimized ET led to better 3D structure-function motifs (3D templates) and, in turn, to enzyme function prediction by the Evolutionary Trace Annotation (ETA) method with better sensitivity of (40% to 53%) and positive predictive value (93% to 94%). This suggests that the similarity of evolutionary importance among neighboring residues in the sequence and in the structure is a universal feature of protein evolution. In practice, this yields a tool for optimizing sequence selections for comparative analysis and, via ET, for better predictions of functional site and function. This should prove useful for the efficient mutational redesign of protein function and for pharmaceutical targeting.

show abstract

Section: Residue Ranking Methodsmentioning

confidence: 99%

Section: Residue Ranking Methodsmentioning

confidence: 99%

Section: Correlations With Deleterious Sequence Perturbationsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation

et al. 2010

Self Cite

View full text Add to dashboard Cite

show abstract

“…Real-valued ET combines ET with sequence entropy. This hybrid method is an enhanced way to rank to the importance of residues to a protein and its family 71 . The residues that real-valued ET ranks as the 10% of most importance are colored green in Figure 5.…”

Section: Internal Network Identified By Sequence Analysismentioning

confidence: 99%

Solution Structure of Inhibitor-Free Human Metalloelastase (MMP-12) Indicates an Internal Conformational Adjustment

Bhaskaran

Palmier

Bagegni

et al. 2007

Journal of Molecular Biology

View full text Add to dashboard Cite

Macrophage metalloelastase or MMP-12 appears to exacerbate atherosclerosis, emphysema, aortic aneurysm, rheumatoid arthritis, and inflammatory bowel disease. An inactivating E219A mutation, validated by crystallography and NMR spectra, prevents autolysis of MMP-12 and allowed us to determine its NMR structure without an inhibitor. The structural ensemble of the catalytic domain without inhibitor is based on 2813 NOEs and has an average RMSD to the mean of 0.25 Å for the backbone and 0.61 Å for all heavy atoms for residues Trp109 -Gly263. Compared to crystal structures of MMP-12, helix B (hB) at the active site is unexpectedly more deeply recessed under the betasheet. This opens a pocket between hB and β-strand sIV in the active site cleft. Both hB and an internal cavity are shifted toward β-strands sI and sIII and hA on the back side of the protease. About 25 internal NOE contacts distinguish the inhibitor-free solution structure and indicate hB's greater depth and proximity to the sheet and hA. Line broadening and multiplicity of amide proton NMR peaks from hB are consistent with hB undergoing slow conformational exchange among subtly different environments. Inhibitor binding-induced perturbations of NMR spectra of MMP-1 and -3 map to similar locations across MMP-12 and encompassing its internal conformational adjustments. Evolutionary trace analysis suggests a functionally important network of residues that encompasses most of the locations that adjust in conformation, including 18 residues with NOE contacts unique to inhibitor-free MMP-12. The conformational change, sequence analysis, and inhibitor perturbations of NMR spectra agree in the network they identify between structural scaffold and active site of MMPs.

show abstract

Prediction of Protein‐Protein Interactions from Evolutionary Information

Valencia

Pazos

2003

Structural Bioinformatics

View full text Add to dashboard Cite

A Family of Evolution–Entropy Hybrid Methods for Ranking Protein Residues by Importance

Cited by 281 publications

References 35 publications

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation

Sequence and structure continuity of evolutionary importance improves protein functional site discovery and annotation

Solution Structure of Inhibitor-Free Human Metalloelastase (MMP-12) Indicates an Internal Conformational Adjustment

Prediction of Protein‐Protein Interactions from Evolutionary Information

Contact Info

Product

Resources

About