Induced conformational transitions

Grubmiiller described a method to induce conformational transitions in proteins and derived rate constants for these ([Grubmiiller 1994]). The method employs subsequent modifications of the original potential function based on a principal component analysis of a short MD simulation. It is discussed in more detail in the chapter of Eichinger et al. in this volume. 

The study of slow protein dynamics is a fascinating field with still many unknowns. We have presented a number of computational techniques that are currently being used to tackle those questions. Most promising for our case seems the development of methods that combine an implicit solvent description with techniques to induce conformational transitions. 

Grinberg, V.Y., Grinberg, N.V., Burova, T.V., Dalgalarrondo, M., and Haertle, T., Ethanol-induced conformational transitions in holo-a-lactalbumin Spectral and calorimetric studies. Biopolymers, 46(4), 253-265, 1998. 

The membrane-bound preparation from kidney is easily solubilized in non-ionic detergent and analytical ultracentrifugation shows that the preparation consists predominantly (80 85%) of soluble af units with 143000 [28]. The soluble a)S unit maintains full Na,K-ATPase activity, and can undergo the cation or nucleotide induced conformational transitions that are observed in the membrane-bound preparation. A cavity for occlusion of 2K or 3Na ions can be demonstrated within the structure of the soluble a)S unit [29], as an indication that the cation pathway is organized in a pore through the aji unit rather than in the interphase between subunits in an oligomer. 

Paoletti, S., Cesaro, A., and Delben, F., Thermally induced conformational transition of xanthan polysaccharide, Carb. Res., 123, 173, 1983. 

Cross-linking constrains the conformational flexibility of biopolymers and, as a rule, stabilizes their secondary, tertiary, and quaternary structures against the denaturing effects of high temperatures.29 We used differential scanning calorimetry (DSC) to compare the heat-induced conformational transitions of selected RNase A samples that were characterized in Figure 15.2. A brief introduction to DSC is provided in Section 15.15.1 for those readers unfamiliar with this biophysical method. Trace 1 in Figure 15.3a is the heat absorption... 

One such property, as has been demonstrated (see [26]), is the change in partial heat capacity of the copolymer solution upon the heat-induced conformational transition of macromolecules. Such a change was detected by high-sensitivity differential scanning calorimetry (HS-DCS). The DSC data for the NVCl/NVIAz-copolymers synthesized at initial comonomer ratios of 85 15 and 90 10 (mole/mole) are given as thermograms in Fig. 4. 

Zhang M, Tanaka T, and Ikura M [ 1995] Calcium-induced conformational transition revealed by the solution structure of apo calmodulin. Nat Struct Biol 2 758-767... 

Herzberg, O., Moult, J., and James, M. N. (1986). A model for the Ca2+-induced conformational transition of troponin C. A trigger for muscle contraction. / Biol. Chem. 261, 2638-2644. 

In order to calculate ensemble averages the explicit time-dependence of the exciton Hamiltonian is replaced by stochastic processes. If drastic changes of Jmn appear due to CC conformational transitions it is hard to apply this approach (Refs. [33] and [34] introduced a dichotomically fluctuating transfer coupling to cover such large conformational transitions). Instead, as it will be demonstrated here, it is more appropriate to directly generate the time-dependence of the exciton parameters Em and Jmn by MD simulations. Then, a microscopic account for solvent effects as well as a detailed description of solvent induced conformational transitions is possible. 

UV Light-induced Conformational Transitions in Azobenzene-containing Polypeptides... 

Sunlight-induced Conformational Transitions in Spiropyran-containing Polypeptides 13.2.2.1 Spiropyran-modified Poly(L-glutamate)s... 

Circular Dichroism and Saccharide-Induced Conformational Transitions of Soybean Agglutinin... 

Peng, X.N., Shao, Z.Z., Chen, X., Knight, D.P., Wu, P.Y., and Vollrath, F. "Further investigation on potassium-induced conformation transition of Nephila spidroin film with two-dimensional infrared correlation spectroscopy". Biomacromolecules 6(1), 302-308... 

Examples of biochemical processes successfully studied by spectroscopic monitoring and multivariate resolution techniques include protonation and complexation of nucleic acids and other events linked to these biomolecules, such as drug intercalation processes and salt, solvent, or temperature-induced conformational transitions [90-97], In general, any change (thermodynamic or structural) that these biomolecules undergo is manifested through a distinct variation in an instrumental signal (usually spectroscopic) and can be potentially analyzed by multivariate resolution techniques. 

The internal motion of T4 lysozyme in the crystal was interpreted as an inter-domain motion corresponding to opening and closing of the active site cleft (Weaver et al., 1989). Hinge-bending and substrate-induced conformational transition in T4 lysozyme in solution were confirmed in a study by site-directed labelling (Mchaourban et al., 1997). 

Native DNAs and polynucleotides can be stretched out as films or fibers. Sealed inside cells with IR transparent windows or in glass capillaries for Raman studies, films and fibers may be expo.sed to an atmosphere with a controlled relative humidity. This is achieved by simply placing small vessels with known saturated salt solutions at the bottom of the cell or by bringing them in contact with the capillary. Changing the relative humidity induces conformational transitions in the sample (Secs. 4.7.1.3.1 and 4.7.1.3.2). Raman studies of polynucleotides have thus been correlated with X-ray diffraction results obtained from the same fibers (Erfurth et al., 1975 Goodwin and Brahms, 1978). 

A. Cesaro, A. Ciana, T. Delben, G. Manzini and S. Paoletti, Physicochemical Properties of Pectic Acid. I. Thermodynamic Evidence of a pH-Induced Conformational Transition in Aqueous Solution. Biopolymers Biopolymers, 21 (1982) 431. 

Particular interest in poly(methacrylic acid), (PMA), has arisen because it represents the first clear example of a S5mthetic vinyl poly-electrol57te whose chain can undergo in aqueous solution a pH-induced conformational transition of distinctly cooperative character. Furthermore, to the author s knowledge, PMA is the only vinyl polyelectrol5de available in samples with a different degree and t5q)e of stereoregularity. Such samples have been prepared and examined in detail. 

Nar, H., Messerschmidt, A., Huber, R., et al. (1991) Crystal structure analysis of oxidized Pseudomonas aeruginosa azurin at pH 5.5 and pH 9.0. ApH-induced conformational transition involves a peptide bond flip. J. Mol. Biol., 221(3), 765-772. 

Cesaro, A., Ciana, A., Delben, F., Manzini, G. and Paoletti, 1982. Thermodynamic evidence of a pH-induced conformational transition in aqueous solution, Biopolymers, 21 431449. 

Ruth. A.. Stein. W.D., Rose, E.. and Roninson, LB. (2001) Coordinate changes in drug resistance and drug-induced conformational transitions in altered-function mutants of the multidrug transporter P-glycoprotein. Biochemistry, 40 (14), 4332-4339. 

Water soluble synthetic polyelectrolytes have attracted increasing attention in recent years, mainly because of their wide utility in industrial applications, and also because of their resemblance to biopolymers. PolyCmethacrylic acid), PMA, a wea)c polyelectrolyte, exhibits a mar)ced pH induced conformational transition. A wide variety of techniques have been employed to gain more information on the nature of the conformational transition of PMA, these techniques include viscometry, potential titrimetry,(1-5) Raman spectrometry,(6) calorimetry,(7-9) electrical conductometry,(10) dilatometry,(11) H NMR linewidth,(12) viscoelastic studies,(13) )cinetics of chemical reactions, (14) small-angle neutron scattering,(15) pH jump,(16,17) and fluorescent probing.(18-27)... 

Langella E, Improta R, Barone V (2004) Checking the pH-induced conformational transition of prion protein by molecular dynamics simulations effect of protonation of histidine residues. Biophys J 87 3623... 

The effect on the conformational-aggrega-tlonal properties of pectate in aqueous solution brought by the addition of specific ions (H+, Ca +. Cu +) was studied by osmometric, microcalorimetric, dilato-metric, and rheological methods. Evidence is provided for the intramolecular nature of the pH induced conformational transition. The addition of divalent ions brings about at the same time a conformational change of the chain of pectate and chain-chain association. 

The results presented here on pectate solutions containing calcium or copper ions bring interesting evidence for an anomalous behavior of pectate properties in the range of ion to polymer ratio below that corresponding to the massive phase separation. The possibility that a conformational change proceeds along with the interaction with divalent ions is examined and discussed in comparison with the case of the proton-induced conformational transition. 

---