References of "Helms, V."
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See detailMolecular dynamics simulation of truncated bovine adrenodoxin
Shakya, S. K.; Gu, Wei UL; Helms, V.

in Biopolymers (2005), 78(1), 9-20

The 128 amino acid long soluble protein adrenodoxin (Adx) is a typical member of the ferredoxin protein family that are electron carrier proteins with an iron-sulfur cofactor. Adx carries electrons from ... [more ▼]

The 128 amino acid long soluble protein adrenodoxin (Adx) is a typical member of the ferredoxin protein family that are electron carrier proteins with an iron-sulfur cofactor. Adx carries electrons from adrenodoxin reductase (AdR) to cytochrome P450s. Its binding modes to these proteins were previously characterized by site-directed mutagenesis, by X-ray crystallography for the complex Adx:AdR, and by NMR. However, no clear evidence has been provided for the driving force that promotes Adx detachment from AdR upon reduction. Here, we characterized the conformational dynamics of unbound Adx in the oxidized and reduced forms using 2-20 ns long molecular dynamics simulations. The most noticeable difference between both forms is the enhanced flexibility of the loop (47-51) surrounding the iron-sulfur cluster in the reduced form. Together with several structural displacements at the binding interface, this increased flexibility may be the key factor promoting unbinding of reduced Adx from AdR. This points to an intrinsic property of reduced Adx that drives dissociation. (c) 2005 Wiley Periodicals, Inc. [less ▲]

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See detailAre solvation free energies of homogeneous helical peptides additive?
Staritzbichler, R.; Gu, Wei UL; Helms, V.

in Journal of Physical Chemistry B (2005), 109(40), 19000-19007

We investigated the additivity of the solvation free energy of amino acids in homogeneous helices of different length in water and in chloroform. Solvation free energies were computed by ... [more ▼]

We investigated the additivity of the solvation free energy of amino acids in homogeneous helices of different length in water and in chloroform. Solvation free energies were computed by multiconfiguration thermodynamic integration involving extended molecular dynamics simulations and by applying the generalized-born surface area solvation model to static helix geometries. The investigation focused on homogeneous peptides composed of uncharged amino acids, where the backbone atoms are kept fixed in an ideal helical conformation. We found nonlinearity especially for short peptides, which does not allow a simple treatment of the interaction of amino acids with their surroundings. For homogeneous peptides longer than five residues, the results from both methods are in quite good agreement and solvation energies are to a good extent additive. [less ▲]

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See detailCyclophilin a binds to linear peptide motifs containing a consensus that is present in many human proteins
Piotukh, K.; Gu, Wei UL; Kofler, M. et al

in Journal of Biological Chemistry (2005), 280(25), 23668-23674

Cyclophilin A ( CypA) is a peptidyl-prolyl cis/trans-isomerase that is involved in multiple signaling events of eukaryotic cells. It might either act as a catalyst for prolyl bond isomerization, or it can ... [more ▼]

Cyclophilin A ( CypA) is a peptidyl-prolyl cis/trans-isomerase that is involved in multiple signaling events of eukaryotic cells. It might either act as a catalyst for prolyl bond isomerization, or it can form stoichiometric complexes with target proteins. We have investigated the linear sequence recognition code for CypA by phage display and found the consensus motif FGPXLp to be selected after five rounds of panning. The peptide FGP-DLPAGD showed inhibition of the isomerase reaction and NMR chemical shift mapping experiments highlight the CypA interaction epitope. Ligand docking suggests that the peptide was able to bind to CypA in the cis- and trans-conformation. Protein Data Bank searches reveal that many human proteins contain the consensus motif, and several of these protein motifs are shown to interact with CypA in vitro. These sequences represent putative target sites for binding of CypA to intracellular proteins. [less ▲]

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See detailAlternative binding modes of proline-rich peptides binding to the GYF domain
Gu, Wei UL; Kofler, M.; Antes, I. et al

in Biochemistry (2005), 44(17), 6404-6415

Recognition of proline-rich sequences plays an important role for the assembly of multiprotein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that ... [more ▼]

Recognition of proline-rich sequences plays an important role for the assembly of multiprotein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that share characteristic features. The GYF (glycine-tyrosine-phenylalanine) domain is known as a member of the superfamily of recognition domains for proline-rich sequences. Recent studies on the complexation of the CD2BP2-GYF domain with CD2 peptides showed that the peptide adopts an extended conformation and forms a polyproline type-II helix involving residues Pro4-Pro7 [Freund et al. (2002) EMBO J. 21, 5985-5995]. R/K/GxxPPGxR/K is the key signature for the peptides that bind to the GYF domain [Kofler et at. (2004) J. Biol. Chem. 279, 28292-28297]. In our combined theoretical and experimental study, we show that the peptides adopt a polyproline 11 helical conformation in the unbound form as well as in the complex. From molecular dynamics simulations, we identify a novel binding mode for the G8W mutant and the wild-type peptide (shifted by one proline in register). In contrast, the conformation of the peptide mutant H9M remains close to the experimentally derived wild-type GYF-peptide complex. Possible functional implications of this altered conformation of the bound ligand are discussed in the light of our experimental and theoretical results. [less ▲]

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See detailDynamical binding of proline-rich peptides to their recognition domains
Gu, Wei UL; Helms, V.

in Biochimica et Biophysica Acta-Proteins and Proteomics (2005), 1754(1-2), 232-238

Recognition of proline-rich sequences plays an important role for the assembly of multi-protein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that ... [more ▼]

Recognition of proline-rich sequences plays an important role for the assembly of multi-protein complexes during the course of eukaryotic signal transduction and is mediated by a set of protein folds that share characteristic features. For many complex systems containing proline-rich sequences, multiple binding modes have been found by theoretical and/or experimental studies. In this review, we discuss the different binding modes as well as the correlated dynamics of the peptides and their recognition domains, and some implications to their biological functions. Further-more, we give an outlook of the systems in the context of systems biology. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

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See detailSolvation free energies and transfer free energies for amino acids from hydrophobic solution to water solution from a very simple residue model
Gu, Wei UL; Rahi, S. J.; Helms, V.

in Journal of Physical Chemistry B (2004), 108(18), 5806-5814

Solvation free energies of neutral amino acids in water and in chloroform were computed from extensive molecular dynamics simulations using multiconfiguration thermodynamic integration. The values ... [more ▼]

Solvation free energies of neutral amino acids in water and in chloroform were computed from extensive molecular dynamics simulations using multiconfiguration thermodynamic integration. The values computed for the AMBER force field are in very good agreement with available experimental data (rms differences of 5.1 kJ mol(-1) for the solvation free energies and 6.4 kJ mol(-1) for the transfer free energies of amino acids between water and chloroform) and with existing calculations. We derived an additive residue-scale solvation model formulated as the sum of a nonpolar term that is proportional to the molecular surface area and an electrostatic term (Kirkwood-Onsager model) for the hydration free energy of a dipole in a solvated cavity. This model can surprisingly well describe the solvation free energies in water and chloroform as well as the transfer free energies of amino acids between the two solvents when suitably adapted cavity radii are used. Root-mean-square differences of the predicted values with respect to the values calculated from thermodynamic integration are 1.8, 5.9, and 7.7 kJ mol(-1), respectively. [less ▲]

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