Intramolecular forces structural effects

Inter- and intramolecular forces (imf) are of vital importance in the quantitative description of structural effects on bioactivities and chemical properties. They can make a significant contribution to chemical reactivities and some physical properties as well. Types of intermolecular forces and their present parameterization are listed in Table 750. 

A number of different molecular mechanisms can underpin the loss of biological activity of any protein. These include both covalent and non-covalent modification of the protein molecule, as summarized in Table 3.20. Protein denaturation, for example, entails a partial or complete alteration of the protein s 3-D shape. This is underlined by the disruption of the intramolecular forces that stabilize a protein s native conformation, viz hydrogen bonding, ionic attractions and hydrophobic interactions. Covalent modifications of protein structure that can adversely effect its biological activity are summarized below. 

Thus, in cases when weak interactions can affect the molecular geometry, the packing of the molecules in the crystal lattice and the solvent effect acquire an important role. In solutions a structure may exist which differs from that achieved in the gaseous phase under the action of intramolecular forces only. 

Elevated pressures can induce functional and structural alterations of proteins. The effects of pressure are governed by Le Chatelier s principle. According to this principle, an increase in pressure favours processes which reduce the overall volume of the system, and conversely increases in pressure inhibit processes which increase the volume. The effects of pressure on proteins depend on the relative contribution of the intramolecular forces which determine their stability and functions. Ionic interactions and hydrophobic interactions are disrupted by pressure. On the other hand, stacking interactions between aromatic rings and charge-transfer interactions are reinforced by pressure. Hydrogen bonds are almost insensitive to pressure. Thus, pressure acts on the secondary, tertiary, and quaternary structure of proteins. The extent and the reversibility, or irreversibility, of pressure effects depend on the pressure range, the rate of compression, and the duration of exposure to increased pressures. These effects are also influenced by other environmental parameters, such as the temperature, the pH, the solvent, and the composition of the medium. 

Pseudomonas aeruginosa (P.a.) azurin has been ruthenated at His-83 (r 11.8 A) (54, 93, 113) the donor-acceptor separation is pictured in Fig. 19. Production of a5Ru(His-83) -Az(Cu ) was achieved by flash photolysis in the presence of [Ru(bpy)3]. The reduction of the protein was monitored at 625 nm, and the intramolecular Ru(II)-to-Cu(II) ET rate of 1.9 s was found to be independent of temperature. The Cu reorganization enthalpy was estimated to be <7 kcal mol (93, 113), a value confirming that blue copper is structured for efficient ET. Table XI compares ET rates for the blue copper proteins with those for heme proteins the blue copper rates are low in comparison with the heme protein rates over similar distances and driving forces. This effect could be a result of poor electronic coupling of asRu with the copper center, possibly owing to unfavorable ET pathways. 

If cavitation occurs at a low intensity, the effectiveness of cavitation will be much reduced. The intramolecular forces within a solvent determine the level of sonication that will drive a bubble to cavitation. Thus it is necessary to choose a solvent that has strong structural cohesion, such as through hydrogen bonding, and high surface tension. Water is clearly the best candidate from this point of... 

The first derivatives and in Eq. (4) vanish at the exact equilibrium geometry of the dimer. But even if we determine first the monomer equilibrium structures, in the intramolecular force fields, and next the dimer equilibrium geometry from the intermolecular potential in Eq. (4), they are very small. Moreover, they have no effect on the vibrational frequencies in first order perturbation theory. In second order they will lead to further, but small, shifts of the monomer frequencies, which we have not calculated. 

A somewhat different opinion on the reason for the the above-discussed disparity between activation barriers was expressed in Ref. [91] to the effect that a dimer may be compressed in crystal packing in order to maintain its structure on balance of inter- and intramolecular forces. Thus, the equilibrium structure of the dimer in the crystal may differ from that in the isolated state . Calculations by a molecular mechanics method gave some substance to this assumption the O O distance in a dimer was shown to be compressed approximately 0.03-0.04 A in the crystal in comparison with an isolated dimer. As a result, the calculated activation barrier is reduced though not so drastically. 

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