Conformations electrostatic interactions

An understanding of a wide variety of phenomena concerning conformational stabilities and molecule-molecule association (protein-protein, protein-ligand, and protein-nucleic acid) requires consideration of solvation effects. In particular, a quantitative assessment of the relative contribution of hydrophobic and electrostatic interactions in macromolecular recognition is a problem of central importance in biology. 

Although the nature of the general polar effect suggested by Kamernitzsky and Akhrem " to account for axial attack in unhindered ketones is not clear, several groups have reported electrostatic interactions affect the course of borohydride reductions. Thus the keto acid (5a) is not reduced by boro-hydride but its ester (5b) is reduced rapidly further, the reduction of the ester (6b) takes place much more rapidly than that of the acid (6a). Spectroscopic data eliminate the possibility that in (5a) there is an interaction between the acid and ketone groups (e.g. formation of a lactol). The results have been attributed to a direct repulsion by the carboxylate ion as the borohydride ion approaches. " By contrast, House and co-workers observed no electrostatic effect on the stereochemistry of reduction of the keto acid (7). However, in this compound the acid group may occupy conformations in which it does not shield the ketone. Henbest reported that substituting chlorine... 

The second part of lanosterol biosynthesis is catalyzed by oxidosqualene lanosterol cyclase and occurs as shown in Figure 27.14. Squalene is folded by the enzyme into a conformation that aligns the various double bonds for undergoing a cascade of successive intramolecular electrophilic additions, followed by a series of hydride and methyl migrations. Except for the initial epoxide protonation/cyclization, the process is probably stepwise and appears to involve discrete carbocation intermediates that are stabilized by electrostatic interactions with electron-rich aromatic amino acids in the enzyme. 

Hogeveen138 measured apparent acidity constants of substituted /i-phenylthio-, /J-phenylsulfinyl- and / -phenylsulfonyl-acrylic acids (cis and trans) in 50% v/v ethanol. The p values for transmission through SCH=CH, SOCH=CH and S02CH=CH were 0.531, 0.389 and 0.320 respectively for the cis acids and 0.652, 0.282 and 0.331 for the trans acids. These results were discussed in considerable detail and compared with those of pertinent related systems. Little importance was attached to the small differences between p values for cis/trans isomers, and the relative transmissions were taken as the mean p values 0.59,0.34 and 0.33. The superior transmission of SCH=CH was attributed to greater polarizability. The values for pKJtrans) — pKJcis) of isomeric acids were also discussed. For the sulfonyl acids this is almost constant at 0.1 unit for the sulfinyl adds there is some variation about a mean value of 0.26 unit, and for the thio adds there is also some variation about a mean value of — 0.15 unit. The differing behavior of the three systems in this respect was explained in terms of hypothetical conformations and electrostatic interactions therein. 

The ionic strength dependence of intrinsic viscosity is function of molecular structure and protein folding, ft is well known that the conformational and rheological properties of charged biopolymer solutions are dependent not only upon electrostatic interactions between macromolecules but also upon interactions between biopolymer chains and mobile ions. Due electrostatic interactions the specific viscosity of extremely dilute solutions seems to increase infinitely with decreasing ionic concentration. Variations of the intrinsic viscosity of a charged polyampholite with ionic strength have problems of characterization. 

Fig. 2.16 Effect of electrostatic interactions on 3i4-helix formation in an aqueous environment [1 75 a, 175 b, 176]. y -Peptides 86 and 87 adopt a stable helical conformation mediated by salt bridges near neutral pH. While the propensity of these peptides to adopt a helical conformation is strongly de-...

From conformational analysis it appears that there is no signifiant influence of the methoxyl group on the conformational behaviour [31,32] only the role of the carboxylic group on the long range electrostatic interaction must be important... 

Another interesting application area of PHMD simulations is to investigate electrostatic interactions in the unfolded states of proteins. A traditional view that unfolded proteins adopt random conformational states that are devoid of electrostatic and hydrophobic interactions, are recently challenged by experimental data [20, 69], REX-CPHMD folding simulations of the 35 residue C-terminal subdomain of the villin headpiece domain revealed a significant deviation from the standard pKa values for several titratable residues. Additional simulations, in which a charged group is neutralized confirmed the existence of specific electrostatic interactions in the unfolded states (JK and CLB, manuscript in preparation). 

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