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Computational Studies of the Effect of Shock Waves on the Binding of Model Complexes.

Kaminski GA - J Chem Theory Comput (2014)

Bottom Line: The behavior of the protein systems was more complex, yet significant disruption of the binding and geometry was also observed.The rationale of the studies was in attempting to understand the strong effects that irradiation with a low-intensity ultrasound can have on biomolecular systems, because such ultrasound irradiation can cause cavitation bubbles to be produced and collapse, thus leading to local shock wave generation.The long-term objective is to contribute to future design of synergetic ultrasound and chemical drug strategy of protein inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute , Worcester, Massachusetts 01609, United States.

ABSTRACT
We have simulated effects of a shock wave in water that would result from the collapse of a cavitation bubble on binding in model complexes. We have considered a benzene dimer, a pair of uracil molecules, a complex of fragments of the X-linked inhibitor of apoptosis and caspase-9, and a fragment of c-Myc oncoprotein in binding with its dimerization partner Max. The effect of the shock waves was simulated by adding a momentum to a slab of solvent water molecules and observing the system as the slab moved and caused changes. In the cases of the small molecular pairs, the passage of the shock waves lead to dissociation of the complexes. The behavior of the protein systems was more complex, yet significant disruption of the binding and geometry was also observed. In all the cases, the effects did not occur during the immediate impact of the high-momentum solvent molecules, but rather during the expansion of the compressed system that followed the passage of the waves. The rationale of the studies was in attempting to understand the strong effects that irradiation with a low-intensity ultrasound can have on biomolecular systems, because such ultrasound irradiation can cause cavitation bubbles to be produced and collapse, thus leading to local shock wave generation. The long-term objective is to contribute to future design of synergetic ultrasound and chemical drug strategy of protein inhibition.

No MeSH data available.


Related in: MedlinePlus

Evolutionof the binding energy in the solvated c-Myc–Maxsimulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.
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fig20: Evolutionof the binding energy in the solvated c-Myc–Maxsimulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.

Mentions: The solute–solute intermolecular bindingenergy of thiszipper-type complex was much lower at the start (see Figure 20), with its equilibrated value being approximately−290 kcal/mol. The compression caused by passage of the shockwave leads to an increase (reduction of magnitude) in this energyof ∼160 kcal/mol. At the same time, the solute–soluteenergy is more negative 20 ps after generation of the wave. At the end of the equilibration, the intermolecular interactionenergy is −297.6 kcal/mol. At the same time, the overall solutepotential energy is −696.5 kcal/mol. At the end of the 520ps simulations, the interaction energy of the dimer is −436.5kcal/mol, while the total energy of the solutes is −382.9 kcal/mol.Thus, the additional potential energy stored as a result of the solutedeformation is (−382.9 + 436.5) – (−696.5 + 297.6)= 452.5 kcal/mol, which is somewhat smaller than in the XIAP–caspase-9case but qualitatively similar to that result. Once again, one canexpect this energy to play a role in either direct dissociation ofthe dimer or in creating altered binding conditions for the complex.


Computational Studies of the Effect of Shock Waves on the Binding of Model Complexes.

Kaminski GA - J Chem Theory Comput (2014)

Evolutionof the binding energy in the solvated c-Myc–Maxsimulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4230379&req=5

fig20: Evolutionof the binding energy in the solvated c-Myc–Maxsimulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.
Mentions: The solute–solute intermolecular bindingenergy of thiszipper-type complex was much lower at the start (see Figure 20), with its equilibrated value being approximately−290 kcal/mol. The compression caused by passage of the shockwave leads to an increase (reduction of magnitude) in this energyof ∼160 kcal/mol. At the same time, the solute–soluteenergy is more negative 20 ps after generation of the wave. At the end of the equilibration, the intermolecular interactionenergy is −297.6 kcal/mol. At the same time, the overall solutepotential energy is −696.5 kcal/mol. At the end of the 520ps simulations, the interaction energy of the dimer is −436.5kcal/mol, while the total energy of the solutes is −382.9 kcal/mol.Thus, the additional potential energy stored as a result of the solutedeformation is (−382.9 + 436.5) – (−696.5 + 297.6)= 452.5 kcal/mol, which is somewhat smaller than in the XIAP–caspase-9case but qualitatively similar to that result. Once again, one canexpect this energy to play a role in either direct dissociation ofthe dimer or in creating altered binding conditions for the complex.

Bottom Line: The behavior of the protein systems was more complex, yet significant disruption of the binding and geometry was also observed.The rationale of the studies was in attempting to understand the strong effects that irradiation with a low-intensity ultrasound can have on biomolecular systems, because such ultrasound irradiation can cause cavitation bubbles to be produced and collapse, thus leading to local shock wave generation.The long-term objective is to contribute to future design of synergetic ultrasound and chemical drug strategy of protein inhibition.

View Article: PubMed Central - PubMed

Affiliation: Department of Chemistry and Biochemistry, Worcester Polytechnic Institute , Worcester, Massachusetts 01609, United States.

ABSTRACT
We have simulated effects of a shock wave in water that would result from the collapse of a cavitation bubble on binding in model complexes. We have considered a benzene dimer, a pair of uracil molecules, a complex of fragments of the X-linked inhibitor of apoptosis and caspase-9, and a fragment of c-Myc oncoprotein in binding with its dimerization partner Max. The effect of the shock waves was simulated by adding a momentum to a slab of solvent water molecules and observing the system as the slab moved and caused changes. In the cases of the small molecular pairs, the passage of the shock waves lead to dissociation of the complexes. The behavior of the protein systems was more complex, yet significant disruption of the binding and geometry was also observed. In all the cases, the effects did not occur during the immediate impact of the high-momentum solvent molecules, but rather during the expansion of the compressed system that followed the passage of the waves. The rationale of the studies was in attempting to understand the strong effects that irradiation with a low-intensity ultrasound can have on biomolecular systems, because such ultrasound irradiation can cause cavitation bubbles to be produced and collapse, thus leading to local shock wave generation. The long-term objective is to contribute to future design of synergetic ultrasound and chemical drug strategy of protein inhibition.

No MeSH data available.


Related in: MedlinePlus