On using oscillating time-dependent restraints in MD simulation

Keller, Bettina G.; Christen, Markus; Oostenbrink, Chris; Gunsteren, Wilfred F. van

doi:10.1007/s10858-006-9081-2

Cited by 15 publications

(17 citation statements)

References 39 publications

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“…[16] For our present purposes it is sufficient to be aware of those effects when analyzing peptide conformations. .…”

Section: Resultsmentioning

confidence: 99%

“…www.chemeurj.org such rapid conformational equilibria and more sophisticated technologies such as ensemble-based or time-dependent restrained MD methods must be utilized. [16] For our present purposes it is sufficient to be aware of those effects when analyzing peptide conformations. The NMR spectrum of the major conformation shows the absence of any (i)H a -(i+1)H a ROE cross peak of the major conformer, indicating that all peptide bonds are trans.…”

Section: Resultsmentioning

confidence: 99%

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Conformational Preference and Potential Templates ofN‐Methylated Cyclic Pentaalanine Peptides

Chatterjee

Mierke

Kessler

2008

Chemistry A European J

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Systematic N-methylation of all peptide bonds in the cyclic pentapeptide cyclo(-D-Ala-Ala(4)-) has been performed yielding 30 different N-methylated derivatives, of which only seven displayed a single conformation on the NMR time scale. The conformation of these differentially N-methylated peptides was recently reported by us (J. Am. Chem. Soc. 2006, 128, 15 164-15 172). Here we present the conformational characterization of nine additional N-methylated peptides from the previous library which are not homogeneous but exist as a mixture in which at least one conformation is preferred by over 80 %. The structures of these peptides are investigated employing various 2D-NMR techniques, distance geometry calculations and further refined by molecular dynamics simulations in explicit DMSO. The comparison of the conformation of these nine peptides and the seven conformationally homogeneous peptides allow us to draw conclusions regarding the influence of N-methylation on the peptide backbone of cyclic pentapeptide of the class cyclo(-D-Ala-Ala(4)-). Here we present the different conformational classes of the peptides arising from the definitive pattern of N-methylation which can eventually serve as templates for the design of bioactive peptides.

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“…[16] For our present purposes it is sufficient to be aware of those effects when analyzing peptide conformations. .…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Conformational Preference and Potential Templates ofN‐Methylated Cyclic Pentaalanine Peptides

Chatterjee

Mierke

Kessler

2008

Chemistry A European J

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“…All samples contained 0.1 mM protein in NMR buffer (20 25,37, and 42°C at 900 MHz. All spectra were processed with NMRPipe (37) and analyzed using CARA (38) or SPARKY3 (version 3.113) (39).…”

Section: Methodsmentioning

confidence: 99%

The Human W42R γD-Crystallin Mutant Structure Provides a Link between Congenital and Age-related Cataracts*

Jung

Koharudin

et al. 2013

Journal of Biological Chemistry

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Background:The mechanism of cataract formation by the recently discovered ␥D-crystallin W42R mutant is unknown. Results: Structural, biochemical, and biophysical studies revealed a partially unfolded species of the W42R mutant. Conclusion: Partially unfolded species serve as nuclei for aggregation. Significance: The properties of the W42R mutant ␥D-crystallin provide the link to the pathogenesis of age-related cataract caused by photodamaged wild-type ␥D-crystallin.

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“…Repetition delays in both experiments were 2 s. Peak intensities were fitted using the CURVEFIT program (A.G. Palmer III, Columbia University). All spectra were processed with NMRPipe (36) and analyzed using CARA (37) or SPARKY3 (version 3.113) (38). Amide 1 H, 15 N- combined chemical shift differences were calculated using Δδ=√((0.15*Δδ N ) 2 +Δδ H 2 ).…”

Section: Methodsmentioning

confidence: 99%

Structural and Biochemical Characterization of the Childhood Cataract-Associated R76S Mutant of Human γD-Crystallin

Jung

Gronenborn

2012

Biochemistry

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Although a number of γD-crystallin mutations are associated with cataract formation, there is not a clear understanding of the molecular mechanism(s) that lead to this protein deposition disease. As part of our ongoing studies on crystallins, we investigated the recently discovered Arg76 to Ser (R76S) mutation that is correlated with childhood cataract in an Indian family. We expressed the R76S γD-crystallin protein in E. coli, characterized it by CD, fluorescence, and NMR spectroscopy, and determined its stability with respect to thermal and chemical denaturation. Surprisingly, no significant biochemical or biophysical differences were observed between the wild-type protein and the R76S variant, except a lowered pI (6.8 compared to the wild-type value of 7.4). NMR assessment of the R76S γD-crystallin solution structure, by RDCs, and of its motional properties, by relaxation measurements, also revealed a close resemblance to wild type crystallin. Further, kinetic unfolding/refolding experiments for R76S and wild-type protein showed similar degrees of off-pathway aggregation suppression by αB-crystallin. Overall, our results suggest that neither structural nor stability changes in the protein are responsible for the R76S γD-crystallin variant's association with cataract. However, the change in pI and the associated surface charge or the altered nature of the amino acid could influence interactions with other lens protein species.

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On using oscillating time-dependent restraints in MD simulation

Cited by 15 publications

References 39 publications

Conformational Preference and Potential Templates ofN‐Methylated Cyclic Pentaalanine Peptides

Conformational Preference and Potential Templates ofN‐Methylated Cyclic Pentaalanine Peptides

The Human W42R γD-Crystallin Mutant Structure Provides a Link between Congenital and Age-related Cataracts*

Structural and Biochemical Characterization of the Childhood Cataract-Associated R76S Mutant of Human γD-Crystallin

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