Proteins folded, intramolecular forces

Many examples exist of highly functional complex nanoscale structures formed via self-assembly processes such as the lipid bilayer membrane, protein folding, DNA and RNA, and viruses (Boeckl and Graham, 2006 Mendes et al., 2013). Although this is a widely observed phenomenon, it is still not fuUy understood. In general, self-assembly is governed by inter- and intramolecular forces to create thermodynamically more stable structures (Boeckl and Graham, 2006). 

The intramolecular forces holding a typical protein in its folded shape are relatively weak, and under conditions of mild heating, a protein can unfold, in a process called denaturation (Figure 25.16). A common example is the cooking of an egg, during which the protein albumin is denatured and changes from a dear solution to a white solid. The secondary and tertiary structures are lost, but the primary structure remains intact. That is, the sequence of amino add... 

The capability of AFM to measure forces in the range of tens of picoNewtons has stimulated its application to study intermolecular and intramolecular forces stabilizing the fold of membrane proteins. The protein of interest is pulled out of the biological membrane by the AFM probe, and the force-distance spectrum depicts the force required to unfold the molecule in distinct steps as well as the contour length of the unfolded pol q)eptide. BR is one of the bestcharacterized membrane proteins by single-molecule force spectroscopy (SMFS). - When force spectroscopy measurements were applied to polytopic membrane proteins, the technique was shown to be sufficiently sensitive to detect forces between the transmembrane helices. - ... 

The resonance-mediated coupling mechanisms described above involve subtle quantal intramolecular/intermolecular donor-acceptor effects that tend to be inadequately described by current-generation empirical potentials. Simulations based on these potentials are therefore likely to be inherently defective for describing realistic folding processes in proteins. However, approximations such as those illustrated in Example 5.8 may ultimately make it feasible to incorporate additional resonance-mediated effects into empirical force fields of tractable form. 

Molecules of globular proteins are folded into compact units that often approach spheroidal shapes. The folding takes place in such a way that the hydro-phobic parts are turned inward, toward each other, and away from water hydrophilic parts—charged groups, for example—tend to stud the surface where they are near water. Hydrogen bonding is chiefly intramolecular. Areas of contact between molecules are small, and intermolecular forces are comparatively weak. 

Tertiary structure involves the intramolecular folding of the polypeptide chain into a compact three-dimensional structure with a specific shape. This structure is maintained by electrovalent linkages, hydrogen bonds, disulfide bridges, van der Waals forces, and hydrophobic interactions. Hydrophobic interactions are considered to be a major force in maintaining the unique tertiary structure of proteins. 

All enzymes are proteins, which are linear sequences of amino acids linked by peptide bonds. The folding of these sequences determined the secondary structure (such as a-helix, p-sheet or p-turn) and tertiary structure. Therefore, the properties of an en me are actually presumed from its sequence of amino acids. Some amino acids, dubbed hot spots , especially the ones in the active site where substrate binds, are sensitive to catalytic properties of an enzyme. Substitution of these important amino acids can significantly improve the activity or enantioselectivity toward a certain reaction. Protein stability is also maintained by the intramolecular and intermolecular interactions between residues of amino acids, including van der Waals forces, hydrophobic forces, electrostatic forces, hydrogen bonds and disulfide bonds. Detailed analysis of these amino acids, usually located in the protein surface, sheds light on the protein design for better thermostability. 

---