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Conformational ensembles explored dynamically from disordered peptides targeting chemokine receptor CXCR4.

Vincenzi M, Costantini S, Scala S, Tesauro D, Accardo A, Leone M, Colonna G, Guillon J, Portella L, Trotta AM, Ronga L, Rossi F - Int J Mol Sci (2015)

Bottom Line: These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles.They revealed a network of transient and dynamic H-bonds and interactions with water molecules.Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. marian.vincenzi@unina.it.

ABSTRACT
This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

No MeSH data available.


The map of MM H-bonds in the 8 and 9 clusters calculated for the PepE (A) and PepK (B), respectively, during MD simulations. We reported with the same colors the residues involved in the same MM H-bonds.
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ijms-16-12159-f005: The map of MM H-bonds in the 8 and 9 clusters calculated for the PepE (A) and PepK (B), respectively, during MD simulations. We reported with the same colors the residues involved in the same MM H-bonds.

Mentions: The number of the most populated clusters resulted as equal to 8 for PepE and 9 for PepK. These clusters are mainly stabilized by MM H-bonds (Figure 5) that involved the atomic groups of the peptide backbone. This structural organization was observed by Pappu et al. [26] for charged peptides: it closely resembles the organization of collapsed and slightly soluble globules.


Conformational ensembles explored dynamically from disordered peptides targeting chemokine receptor CXCR4.

Vincenzi M, Costantini S, Scala S, Tesauro D, Accardo A, Leone M, Colonna G, Guillon J, Portella L, Trotta AM, Ronga L, Rossi F - Int J Mol Sci (2015)

The map of MM H-bonds in the 8 and 9 clusters calculated for the PepE (A) and PepK (B), respectively, during MD simulations. We reported with the same colors the residues involved in the same MM H-bonds.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4490436&req=5

ijms-16-12159-f005: The map of MM H-bonds in the 8 and 9 clusters calculated for the PepE (A) and PepK (B), respectively, during MD simulations. We reported with the same colors the residues involved in the same MM H-bonds.
Mentions: The number of the most populated clusters resulted as equal to 8 for PepE and 9 for PepK. These clusters are mainly stabilized by MM H-bonds (Figure 5) that involved the atomic groups of the peptide backbone. This structural organization was observed by Pappu et al. [26] for charged peptides: it closely resembles the organization of collapsed and slightly soluble globules.

Bottom Line: These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles.They revealed a network of transient and dynamic H-bonds and interactions with water molecules.Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmacy University of Naples "Federico II", and CIRPeB, Via Mezzocannone 16, I-80134 Naples, Italy. marian.vincenzi@unina.it.

ABSTRACT
This work reports on the design and the synthesis of two short linear peptides both containing a few amino acids with disorder propensity and an allylic ester group at the C-terminal end. Their structural properties were firstly analyzed by means of experimental techniques in solution such as CD and NMR methods that highlighted peptide flexibility. These results were further confirmed by MD simulations that demonstrated the ability of the peptides to assume conformational ensembles. They revealed a network of transient and dynamic H-bonds and interactions with water molecules. Binding assays with a well-known drug-target, i.e., the CXCR4 receptor, were also carried out in an attempt to verify their biological function and the possibility to use the assays to develop new specific targets for CXCR4. Moreover, our data indicate that these peptides represent useful tools for molecular recognition processes in which a flexible conformation is required in order to obtain an interaction with a specific target.

No MeSH data available.