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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

Evolution of the binding energy in the solvated XIAP–caspase-9simulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.
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fig17: Evolution of the binding energy in the solvated XIAP–caspase-9simulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.

Mentions: However, the evolution of the dimer was more complexin this case(and the next protein dimer case). The size of the molecules is much larger than that of the benzeneor uracil systems; thus, complete dissociation of the complexes withinthe short time frame of the simulations is not possible. The evolutionof the XIAP–caspase-9 interaction energy is shown in Figure 17. After the peak of ca. 140 kcal/mol, which correspondsto the compression created by the passing shock wavefront, the energyoscillates and seems to settle at a value near −60 kcal/mol,which is not greatly higher than the equilibrium value of approximately−80 kcal/mol for this complex. However, the physical pictureis rather far from the complex returning to its original state. Thegraph in Figure 17 shows the interaction energybetween the molecules and not the total potential energy of the solute.In the cases of the benzene and uracil dimers, the difference betweenthe two was not fundamentally significant, since these solute moleculesare small and do not have any significant possibility of conformationalchange. However, the protein fragments simulated in this part of theproject have a much greater ability to experience changes in the intramolecularconformations. The equilibrated value of the intermolecular energyis approximately −80 kcal/mol, with the total solute energyimmediately before the increase in the linear momentum occurs being−445.8 kcal/mol. At the end of the simulations (t = 520 ps in Figure 17), the intermolecularenergy is −51.4 kcal/mol, but the total potential energy ofthe solute is +149.6 kcal/mol. Therefore, deformation of the solutespermits the storage of additional energy: (149.6 + 51.4) –(−445.8 + 80) = +566.8 kcal/mol. This energy must dissipateeventually, and it is probable that this can lead to either directdissociation of the dimer or to a serious deformation that makes bindingless favorable.


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

Kaminski GA - J Chem Theory Comput (2014)

Evolution of the binding energy in the solvated XIAP–caspase-9simulations. 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

fig17: Evolution of the binding energy in the solvated XIAP–caspase-9simulations. The increase in the momentum of a slab of the solventoccurs at t = 500 ps.
Mentions: However, the evolution of the dimer was more complexin this case(and the next protein dimer case). The size of the molecules is much larger than that of the benzeneor uracil systems; thus, complete dissociation of the complexes withinthe short time frame of the simulations is not possible. The evolutionof the XIAP–caspase-9 interaction energy is shown in Figure 17. After the peak of ca. 140 kcal/mol, which correspondsto the compression created by the passing shock wavefront, the energyoscillates and seems to settle at a value near −60 kcal/mol,which is not greatly higher than the equilibrium value of approximately−80 kcal/mol for this complex. However, the physical pictureis rather far from the complex returning to its original state. Thegraph in Figure 17 shows the interaction energybetween the molecules and not the total potential energy of the solute.In the cases of the benzene and uracil dimers, the difference betweenthe two was not fundamentally significant, since these solute moleculesare small and do not have any significant possibility of conformationalchange. However, the protein fragments simulated in this part of theproject have a much greater ability to experience changes in the intramolecularconformations. The equilibrated value of the intermolecular energyis approximately −80 kcal/mol, with the total solute energyimmediately before the increase in the linear momentum occurs being−445.8 kcal/mol. At the end of the simulations (t = 520 ps in Figure 17), the intermolecularenergy is −51.4 kcal/mol, but the total potential energy ofthe solute is +149.6 kcal/mol. Therefore, deformation of the solutespermits the storage of additional energy: (149.6 + 51.4) –(−445.8 + 80) = +566.8 kcal/mol. This energy must dissipateeventually, and it is probable that this can lead to either directdissociation of the dimer or to a serious deformation that makes bindingless favorable.

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