Escher: A new docking procedure applied to the reconstruction of protein tertiary structure

Ausiello, Gabriele; Helmer‐Citterich, Manuela

doi:10.1002/(sici)1097-0134(199708)28:4<556::aid-prot9>3.3.co;2-c

Cited by 30 publications

(50 citation statements)

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“…Consistent with this model, Cys553 of GCLC was not adducted by 4-HNE when present as GCL holoenzyme, suggesting that the region surrounding Cys553 likely resides within the interaction interface between GCLC and GCLM. Possible interactions between the GCLC and GCLM homology models were examined using Escher NG, which predicts likely protein-protein interactions based on shape complementarity and steric interactions [54]. Many of the resulting interactions involved the region of GCLC containing Cys553 and a representative structure is given in Figure 9C.…”

Section: Resultsmentioning

confidence: 99%

“…Cys residue pKa calculations were determined using the Vega ZZ program [52] with the PROPKA plugin [53]. Likely subunit interactions were predicted with the Escher NG plugin [54] using a probe radius of 1.0 angstrom, rotation step of 5 degrees, and a max collisions/min charge of 300 and -300, respectively. The resulting structures were rendered in Lightwave 3D 9.6 (NewTek Inc., San Antonio, TX) for figure presentation.…”

Section: Methodsmentioning

confidence: 99%

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Posttranslational modification and regulation of glutamate–cysteine ligase by the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal

Backos

Fritz

Roede

et al. 2011

Free Radical Biology and Medicine

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Abstract4-hydroxy-2-nonenal (4-HNE) is a lipid peroxidation product formed during oxidative stress that can alter protein function via adduction of nucleophilic amino acid residues. 4-HNE detoxification occurs mainly via GSH conjugation and transporter-mediated efflux. This results in a net loss of cellular GSH and restoration of GSH homeostasis requires de novo GSH biosynthesis. The ratelimiting step in GSH biosynthesis is catalyzed by glutamate cysteine ligase (GCL), a heterodimeric holoenzyme composed of a catalytic (GCLC) and modulatory (GCLM) subunit. The relative levels of the GCL subunits are a major determinant of cellular GSH biosynthetic capacity and 4-HNE induces the expression of both GCL subunits. In this study, we demonstrate that 4-HNE can alter GCL holoenzyme formation and activity via direct post-translational modification of the GCL subunits in vitro. 4-HNE directly modified Cys553 of GCLC and Cys35 of GCLM in vitro, which significantly increased monomeric GCLC enzymatic activity, but reduced GCL holoenzyme activity and formation of the GCL holoenzyme complex. In silico molecular modeling studies also indicate these residues are likely to be functionally relevant. Within a cellular context, this novel post-translational regulation of GCL activity could significantly affect cellular GSH homeostasis and GSH-dependent detoxification during periods of oxidative stress.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Posttranslational modification and regulation of glutamate–cysteine ligase by the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal

Backos

Fritz

Roede

et al. 2011

Free Radical Biology and Medicine

View full text Add to dashboard Cite

show abstract

“…Of the various scoring functions, the most useful and efficient ones are those based on the ligand–receptor shape complementarity 18, 44–49. Besides geometry functions, other types of functions have been developed and implemented in docking procedures, such as electrostatic interactions,7, 20, 22, 32, 50 atomic hydrophobicity,51, 52 hydrogen bonding terms,16, 53, 54 and more complete evaluations of relative free energy of binding 55, 56. Knowledge‐based scoring functions have also been demonstrated to be helpful 57–66…”

Section: Introductionmentioning

confidence: 99%

Optimized grid‐based protein–protein docking as a global search tool followed by incorporating experimentally derivable restraints

Huang¹

2011

Proteins

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Unbound protein docking, or the computational prediction of the structure of a protein complex from the structures of its separated components, is of importance but still challenging. A practical approach toward reliable results for unbound docking is to incorporate experimentally derived information with computation. To this end, truly systematic search of the global docking space is desirable. The fast Fourier transform (FFT) docking is a systematic search method with high computational efficiency. However, by using FFT to perform unbound docking, possible conformational changes upon binding must be treated implicitly. To better accommodate the implicit treatment of conformational flexibility, we develop a rational approach to optimize "softened" parameters for FFT docking. In connection with the increased "softness" of the parameters in this global search step, we use a revised rule to select candidate models from the search results. For complexes designated as of low and medium difficulty for unbound docking, these adaptations of the original FTDOCK program lead to substantial improvements of the global search results. Finally, we show that models resulted from FFT-based global search can be further filtered with restraints derivable from nuclear magnetic resonance (NMR) chemical shift perturbation or mutagenesis experiments, leading to a small set of models that can be feasibly refined and evaluated using computationally more expensive methods and that still include high-ranking near-native conformations.

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“…We used atomic parameters as described by Ausiello et al28 to obtain a measure of electrostatic complementarity that can be quickly computed. The electrostatic complementarity at the interface was calculated according to eq.…”

Section: Methods and Algorithmsmentioning

confidence: 99%

“…Here, A ( p i , p j ) are statistical interaction energies,28 r ij the distance between atoms i , j ( r max = 4.0 Å if both atoms are apolar, 3.4 Å otherwise).…”

Section: Methods and Algorithmsmentioning

confidence: 99%

Protein‐protein docking by shape‐complementarity and property matching

2010

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We present a computational approach to protein-protein docking based on surface shape complementarity ("ProBinder"). Within this docking approach, we implemented a new surface decomposition method that considers local shape features on the protein surface. This new surface shape decomposition results in a deterministic representation of curvature features on the protein surface, such as "knobs," "holes," and "flats" together with their point normals. For the actual docking procedure, we used geometric hashing, which allows for the rapid, translation-, and rotation-free comparison of point coordinates. Candidate solutions were scored based on knowledge-based potentials and steric criteria. The potentials included electrostatic complementarity, desolvation energy, amino acid contact preferences, and a van-der-Waals potential. We applied ProBinder to a diverse test set of 68 bound and 30 unbound test cases compiled from the Dockground database. Sixty-four percent of the protein-protein test complexes were ranked with an root mean square deviation (RMSD) < 5 A to the target solution among the top 10 predictions for the bound data set. In 82% of the unbound samples, docking poses were ranked within the top ten solutions with an RMSD < 10 A to the target solution.

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Escher: A new docking procedure applied to the reconstruction of protein tertiary structure

Cited by 30 publications

References 0 publications

Posttranslational modification and regulation of glutamate–cysteine ligase by the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal

Posttranslational modification and regulation of glutamate–cysteine ligase by the α,β-unsaturated aldehyde 4-hydroxy-2-nonenal

Optimized grid‐based protein–protein docking as a global search tool followed by incorporating experimentally derivable restraints

Protein‐protein docking by shape‐complementarity and property matching

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