PIPER: An FFT‐based protein docking program with pairwise potentials

Kozakov, Dima; Brenke, Ryan; Comeau, Stephen R.; Vajda, Sándor

doi:10.1002/prot.21117

Cited by 776 publications

(774 citation statements)

References 47 publications

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“…Bioinformatics Analysis-Homology modeling of EcCopA was performed using SWISS-MODEL software (25) ) was analyzed with ClusPro version 2.0 using standard parameters (26,27).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

Padilla‐Benavides

Thompson

McEvoy

et al. 2014

Journal of Biological Chemistry

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“…Bioinformatics Analysis-Homology modeling of EcCopA was performed using SWISS-MODEL software (25) ) was analyzed with ClusPro version 2.0 using standard parameters (26,27).…”

Section: Methodsmentioning

confidence: 99%

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

Padilla‐Benavides

Thompson

McEvoy

et al. 2014

Journal of Biological Chemistry

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“…19 To obtain an Ab dimer (lowest free energy), two of the same monomers were used. The ClusPro2.0 server, one of the top performers at CAPRI (Critical Assessment of Predicted Interactions) round [13][14][15][16][17][18][19]20 was used to predict the possible structure of the oligomers. We submitted to ClusPro two monomers to obtain the dimer, which was used to dock with another monomer to form a trimer, and so forth; this process was performed until an Ab pentamer was formed.…”

Section: Docking Methodsmentioning

confidence: 99%

“…Both structures have the minimal sequence able to form the oligomers. 18 Therefore, the protein-protein docking was first performed with two monomers of each structure to build a dimer (Fig. 7, Set 1, in blue).…”

Section: Molecular Dynamics Simulationsmentioning

confidence: 99%

In silico and in vitro studies to elucidate the role of Cu²⁺ and galanthamine as the limiting step in the amyloid beta (1–42) fibrillation process

et al. 2013

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The formation of fibrils and oligomers of amyloid beta (Aβ) with 42 amino acid residues (Aβ1–42) is the most important pathophysiological event associated with Alzheimer's disease (AD). The formation of Aβ fibrils and oligomers requires a conformational change from an α‐helix to a β‐sheet conformation, which is encouraged by the formation of a salt bridge between Asp 23 or Glu 22 and Lys 28. Recently, Cu2+ and various drugs used for AD treatment, such as galanthamine (Reminyl®), have been reported to inhibit the formation of Aβ fibrils. However, the mechanism of this inhibition remains unclear. Therefore, the aim of this work was to explore how Cu2+ and galanthamine prevent the formation of Aβ1–42 fibrils using molecular dynamics (MD) simulations (20 ns) and in vitro studies using fluorescence and circular dichroism (CD) spectroscopies. The MD simulations revealed that Aβ1–42 acquires a characteristic U‐shape before the α‐helix to β‐sheet conformational change. The formation of a salt bridge between Asp 23 and Lys 28 was also observed beginning at 5 ns. However, the MD simulations of Aβ1−42 in the presence of Cu2+ or galanthamine demonstrated that both ligands prevent the formation of the salt bridge by either binding to Glu 22 and Asp 23 (Cu2+) or to Lys 28 (galanthamine), which prevents Aβ1−42 from adopting the U‐characteristic conformation that allows the amino acids to transition to a β‐sheet conformation. The docking results revealed that the conformation obtained by the MD simulation of a monomer from the 1Z0Q structure can form similar interactions to those obtained from the 2BGE structure in the oligomers. The in vitro studies demonstrated that Aβ remains in an unfolded conformation when Cu2+ and galanthamine are used. Then, ligands that bind Asp 23 or Glu 22 and Lys 28 could therefore be used to prevent β turn formation and, consequently, the formation of Aβ fibrils.

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“…Template-free docking methods rely on the geometric and chemicalphysical complementarity of the protein surfaces (1), now often supplemented by statistical potentials (2,3), and subject to a variety of constraints (4). The template-free modeling can also be applied to prediction of domain-domain structures (5,6).…”

mentioning

confidence: 99%

Templates are available to model nearly all complexes of structurally characterized proteins

Kundrotas

Zhu²,

Janin³

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

179

210

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Traditional approaches to protein-protein docking sample the binding modes with no regard to similar experimentally determined structures (templates) of protein-protein complexes. Emerging template-based docking approaches utilize such similar complexes to determine the docking predictions. The docking problem assumes the knowledge of the participating proteins' structures. Thus, it provides the possibility of aligning the structures of the proteins and the template complexes. The progress in the development of template-based docking and the vast experience in template-based modeling of individual proteins show that, generally, such approaches are more reliable than the free modeling. The key aspect of this modeling paradigm is the availability of the templates. The current common perception is that due to the difficulties in experimental structure determination of protein-protein complexes, the pool of docking templates is insignificant, and thus a broad application of template-based docking is possible only at some future time. The results of our large scale, systematic study show that, surprisingly, in spite of the limited number of proteinprotein complexes in the Protein Data Bank, docking templates can be found for complexes representing almost all the known proteinprotein interactions, provided the components themselves have a known structure or can be homology-built. About one-third of the templates are of good quality when they are compared to experimental structures in test sets extracted from the Protein Data Bank and would be useful starting points in modeling the complexes. This finding dramatically expands our ability to model protein interactions, and has far-reaching implications for the protein docking field in general.protein modeling | protein recognition | structural bioinformatics | structure alignment P rotein-protein interactions (PPI) are a key component of life processes at the molecular level, and the number detected in genome-wide studies is fast growing. We want to understand their properties and be able to manipulate them for structure-based drug design. For this purpose, we must characterize PPI structurally, but their study by X-ray and NMR methods is demanding and slow, and computational methods appear to be a necessary complement.The structural predictions of PPI generally rely on docking procedures that can be roughly divided into: (i) template-free docking, where many or all the possible binding modes of two proteins are explored with no a priori knowledge of the structure of the complex, and (ii) template-based docking, where the similarity with previously known complexes determines the prediction. Template-free docking methods rely on the geometric and chemicalphysical complementarity of the protein surfaces (1), now often supplemented by statistical potentials (2, 3), and subject to a variety of constraints (4). The template-free modeling can also be applied to prediction of domain-domain structures (5, 6). The Critical Assessment of Predicted Interactions (CAPRI) blind predi...

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PIPER: An FFT‐based protein docking program with pairwise potentials

Cited by 776 publications

References 47 publications

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

In silico and in vitro studies to elucidate the role of Cu²⁺ and galanthamine as the limiting step in the amyloid beta (1–42) fibrillation process

Templates are available to model nearly all complexes of structurally characterized proteins

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PIPER: An FFT‐based protein docking program with pairwise potentials

Cited by 776 publications

References 47 publications

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

Mechanism of ATPase-mediated Cu+ Export and Delivery to Periplasmic Chaperones

In silico and in vitro studies to elucidate the role of Cu2+ and galanthamine as the limiting step in the amyloid beta (1–42) fibrillation process

Templates are available to model nearly all complexes of structurally characterized proteins

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In silico and in vitro studies to elucidate the role of Cu²⁺ and galanthamine as the limiting step in the amyloid beta (1–42) fibrillation process