Introducing <scp>P</scp>ep <scp>McConst</scp>—A user‐friendly peptide modeler for biophysical applications

Schuhmann, Fabian; Korol, Vasili; Solov’yov, Ilia A.

doi:10.1002/jcc.26479

Cited by 8 publications

(6 citation statements)

References 23 publications

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“…The alignment process was repeated while aligning the whole structure, and hence not excluding the catalytic domain. Difference distance matrices were computed following the approach outlined earlier [ 35 ], in which every residue was described through the first backbone carbon atom, and the distances to all other seven binding-site residues were measured. These calculated distances were averaged over the duration of the MD simulation.…”

Section: Resultsmentioning

confidence: 99%

“…The peptide modeler Pep McConst [ 35 ] was used to reconstruct the missing residues, followed by structure minimization in a vacuum, in which all residues except the newly added ones were restrained to allow the newly added part to relax to a feasible conformation. Following energy minimization, the structure was first equilibrated with a simulation timestep of 0.25 fs, which was increased to 1.0 fs once a stable conformation was achieved.…”

Section: Methodsmentioning

confidence: 99%

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The Transition of Photoreceptor Guanylate Cyclase Type 1 to the Active State

Shahu

Schuhmann

Scholten

et al. 2022

IJMS

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Membrane-bound guanylate cyclases (GCs), which synthesize the second messenger guanosine-3′, 5′-cyclic monophosphate, differ in their activation modes to reach the active state. Hormone peptides bind to the extracellular domain in hormone-receptor-type GCs and trigger a conformational change in the intracellular, cytoplasmic part of the enzyme. Sensory GCs that are present in rod and cone photoreceptor cells have intracellular binding sites for regulatory Ca2+-sensor proteins, named guanylate-cyclase-activating proteins. A rotation model of activation involving an α-helix rotation was described as a common activation motif among hormone-receptor GCs. We tested whether the photoreceptor GC-E underwent an α-helix rotation when reaching the active state. We experimentally simulated such a transitory switch by integrating alanine residues close to the transmembrane region, and compared the effects of alanine integration with the point mutation V902L in GC-E. The V902L mutation is found in patients suffering from retinal cone–rod dystrophies, and leads to a constitutively active state of GC-E. We analyzed the enzymatic catalytic parameters of wild-type and mutant GC-E. Our data showed no involvement of an α-helix rotation when reaching the active state, indicating a difference in hormone receptor GCs. To characterize the protein conformations that represent the transition to the active state, we investigated the protein dynamics by using a computational approach based on all-atom molecular dynamics simulations. We detected a swinging movement of the dimerization domain in the V902L mutant as the critical conformational switch in the cyclase going from the low to high activity state.

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Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

The Transition of Photoreceptor Guanylate Cyclase Type 1 to the Active State

Shahu

Schuhmann

Scholten

et al. 2022

IJMS

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“…A similar method was introduced in earlier work . Gly–X–Gly tripeptides were constructed with Pep McConst software and simulated for 1 ns in a waterbox using NAMD. MSA values for the X residues were determined using GETAREA2 .…”

Section: Methodsmentioning

confidence: 99%

Dimerization of European Robin Cryptochrome 4a

et al. 2023

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Homo-dimer formation is important for the function of many proteins. Although dimeric forms of cryptochromes (Cry) have been found by crystallography and were recently observed in vitro for European robin Cry4a, little is known about the dimerization of avian Crys and the role it could play in the mechanism of magnetic sensing in migratory birds. Here, we present a combined experimental and computational investigation of the dimerization of robin Cry4a resulting from covalent and non-covalent interactions. Experimental studies using native mass spectrometry, mass spectrometric analysis of disulfide bonds, chemical cross-linking, and photometric measurements show that disulfide-linked dimers are routinely formed, that their formation is promoted by exposure to blue light, and that the most likely cysteines are C317 and C412. Computational modeling and molecular dynamics simulations were used to generate and assess a number of possible dimer structures. The relevance of these findings to the proposed role of Cry4a in avian magnetoreception is discussed.

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“…MSA was computed for the Gly-X-Gly tripeptide (glycine was chosen to introduce the least steric hindrance and allow the largest solvent accessibility). For each of the 20 naturally occurring amino acid residues X, the Gly-X-Gly peptide was constructed using the Pep McConst [58] software and later simulated for 1 ns in water. The SASA values for residue X in the tripeptide and every amino acid residue in the avian cryptochromes were calculated using VMD.…”

Section: Solvent-accessible Surface Area Calculationsmentioning

confidence: 99%

On the energetic differences of avian cryptochromes 4 from selected species

et al. 2022

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Cryptochromes are a class of light-absorbing proteins that have been shown to be a part of the circadian rhythm of many animals but seem to play a central role for the magnetosensing of migratory birds. Following a documented difference in the sensitivity to an external magnetic field of cryptochrome 4a proteins from migratory and non-migratory birds, a detailed analysis of inter- and intra-protein energetics is called for. The present study relies on classical molecular dynamics simulations of cryptochrome 4a from five avian species to reveal if any of the cryptochromes feature peculiarities in their internal energetics. The five avian cryptochrome 4a proteins from pigeon, European robin, zebra finch, chicken, and Eurasian blackcap are found to be highly similar in respect of their intra-energetic behaviors, while some minor differences between the cryptochromes can be ascribed to the site of specific structural differences. Particular attention has been paid to account for the interaction of the protein with the solvent, and it has been revealed that the solvent could lead to significant stabilization of the chromophore flavin adenine dinucleotide inside of the cryptochrome 4a scaffold.

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Introducing Pep McConst—A user‐friendly peptide modeler for biophysical applications

Cited by 8 publications

References 23 publications

The Transition of Photoreceptor Guanylate Cyclase Type 1 to the Active State

The Transition of Photoreceptor Guanylate Cyclase Type 1 to the Active State

Dimerization of European Robin Cryptochrome 4a

On the energetic differences of avian cryptochromes 4 from selected species

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