Conformation stabilizing interaction

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. 

Display electrostatic potential maps for both anti and gauche conformers of 1,2-ethanediol. Do you see any examples of destabilizing interactions (between like charges) or stabilizing interactions (between unlike charges) in either conformer Are you able to explain the observed conformational preference ... 

In 1982 the present author discovered cyclic orbital interactions in acyclic conjugation, and showed that the orbital phase continuity controls acyclic systems as well as the cyclic systems [23]. The orbital phase theory has thus far expanded and is still expanding the scope of its applications. Among some typical examples are included relative stabilities of cross vs linear polyenes and conjugated diradicals in the singlet and triplet states, spin preference of diradicals, regioselectivities, conformational stabilities, acute coordination angle in metal complexes, and so on. 

Marlborough, D.I., Miller, D.S. Cammack, K.A. (1975). Comparative study on conformational stability and sub-unit interactions of two bacterial asparaginases. Biochimica Biophysica Acta, 386, 576-89. 

While loops lack apparent stmcmral regularity, they exist in a specific conformation stabilized through hydrogen bonding, salt bridges, and hydrophobic interactions with other portions of the protein. However, not all portions of proteins are necessarily ordered. Proteins may contain disordered regions, often at the extreme amino or carboxyl terminal, characterized by high conformational flexibility. In many instances, these disor-... 

We note that the calculation of At/ will depend primarily on local information about solute-solvent interactions i.c., the magnitude of A U is of molecular order. An accurate determination of this partition function is therefore possible based on the molecular details of the solution in the vicinity of the solute. The success of the test-particle method can be attributed to this property. A second feature of these relations, apparent in Eq. (4), is the evaluation of solute conformational stability in solution by separately calculating the equilibrium distribution of solute conformations for an isolated molecule and the solvent response to this distribution. This evaluation will likewise depend on primarily local interactions between the solute and solvent. For macromolecular solutes, simple physical approximations involving only partially hydrated solutes might be sufficient. 

O- HOMO — LUMO stabilizing interaction Q conformational j exo-anomericeffect no/... 

Therefore any flexible acetal will undergo conformational changes to permit 2p(0) <-> 2p(C+) stabilizing interaction to intervene in the transition state of its heterolysis. This is also true for pyranosides for which the free energy difference between chair, boat and sofa conformers rarely surpasses 10 kcal/mol. 

Clearly, in the syn conformation there is a stabilizing interaction between the fluorine 2px lone pair and the LUMO of the methyl group. This type of interaction... 

An interesting problem arises when we examine the relative stabilization of the Css and Cee conformations of the model systems dimethyl ether and isobutene. In the former case, there is only one dominant two electron stabilizing interaction which favors the C conformation. On the other hand, in the case of isobutene there are two key two electron stabilizing interactions, one favoring the Css and the other favoring the Cee conformation. These considerations can be best understood by reference to Fig. 29. 

The interaction diagrams for the above conformations are identical with that of methyl vinyl ether (Fig. 30) except that the oxygen lone pair AO is replaced by an unoccupied carbon 2p AO. With this in mind we conclude that the transoid conformation of the cation, Ts, will be more stable than the cisoid conformation, Cs, since the <(>j—Pz two electron stabilizing interaction is greater for the Ts conformation. 

We conclude from the above considerations that pi nonbonded attractive interactions may dominate sigma nonbonded attractive interactions and, consequently, conformational stability in ortho xylene could vary in the following way SS > EE > SE. 

We can extend the above theoretical approach to isoconjugate molecules such as acrolein and glyoxal. Arguing as before, we conclude that the relative order of conformational stability will be gauche > tram > cis if pi nonbonded interactions dictate the preferred conformation, cis > gauche > trans if sigma interactions are dominant, and trans > gauche > cis if steric effects are the most important factor. 

The pi MO s of this system can then be constructed from the pi group MO s spanning the two X groups in a cis or tram conformation and the cis or tram pi MO manifolds of the butadienic fragment. These constructions are illustrated by means of the interaction diagram of Fig. 33. Proceeding as before we now compare the stabilizing interactions for the cis and tram conformations. 

The n—7r stabilizing interaction which obtains in each conformation is listed above. Since the oxygen 2p lone pair AO is a better intrinsic donor orbital than the oxygen hybrid sp2 lone pair AO, we conclude that n—tt interactions favor the conformation in which all atoms are contained in the same plane. 

In the eclipsed conformation the stabilizing interaction is ocx — p+ and in the perpendicular conformation the principal stabilizing interaction is the 0ch P+ interaction. Arguing as before we conclude the following ... 

We first examine the case of piperidine. The two conformations, axial and equatorial are shown below along with an enumeration of the major stabilizing interactions, if we only consider vicinal bonds. 

The third class of host defense peptides, the extended peptide class, is defined by the relative absence of a defined secondary structure. These peptides normally contain high proportions of amino acids such as histidine, tryptophan, or proline and tend to adopt an overall extended conformation upon interaction with hydrophobic environments. Examples of peptides belonging to the extended class include indolicidin, a bovine neutrophil peptide, and the porcine peptide fragment, tritpticin. These structures are stabilized by hydrogen bonding and van der Waals forces as a result of contact with lipids in contrast to the intramolecular stabilization forces found in the former peptide classes. 

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