Solvent protein model

The first term represents the forces due to the electrostatic field, the second describes forces that occur at the boundary between solute and solvent regime due to the change of dielectric constant, and the third term describes ionic forces due to the tendency of the ions in solution to move into regions of lower dielectric. Applications of the so-called PBSD method on small model systems and for the interaction of a stretch of DNA with a protein model have been discussed recently ([Elcock et al. 1997]). This simulation technique guarantees equilibrated solvent at each state of the simulation and may therefore avoid some of the problems mentioned in the previous section. Due to the smaller number of particles, the method may also speed up simulations potentially. Still, to be able to simulate long time scale protein motion, the method might ideally be combined with non-equilibrium techniques to enforce conformational transitions. 

The final class of methods that we shall consider for calculating the electrostatic compone of the solvation free energy are based upon the Poisson or the Poisson-Boltzmann equatior Ihese methods have been particularly useful for investigating the electrostatic properties biological macromolecules such as proteins and DNA. The solute is treated as a body of co stant low dielectric (usually between 2 and 4), and the solvent is modelled as a continuum high dielectric. The Poisson equation relates the variation in the potential (f> within a mediu of uniform dielectric constant e to the charge density p ... 

Hbp C93 S-nitrosation could also be accomplished by exposure to RSNOs (GSNO or CysNO). The rates RSNO-dependent Hb-S-nitrosation was 10-fold larger in oxy-Hb than in deoxy-Hb. Conversely, the rate of spontaneous decay of deoxy-Hb-SNO was -20-fold larger than oxy-Hb-SNO. An explanation for this differential reactivity was presented in a subsequent study (Stamler et al, 1997) where protein modeling data based on the X-ray structures of Hb in T and R states indicated that in OxyHb the SNO of Cys (1 93 is protected from solvent. In contrast, in deoxyHb the SNO is highly exposed to solvent. The implication was that the NO+ on Cys (193-S-NO could be transferred to thiols in RBC and eventually effluxed to induce vasodilation under conditions of low 02 saturation. 

To explain the observed optical induction, a substrate was incorporated into the molecular model of the protein. A substrate such as a-ketoglutarate could be included in the protein model with a geometry that allowed stereoselective protonation of the quinoid intermediate by solvent, consistent with the enantiomeric excess (ee) of the 1-stereoisomer product. Moreover, the geometry consistent with production of the d-enantiomer appeared too sterically crowded for most substrates. However, pyruvic acid, which was the only substrate to favor the d-enantiomer product, was small enough to adopt the alternative geometry and also had the potential to interact with an arginine group. 

Figure 11.3 The ratio of the number of reflections to the number of parameters in the XYZB crystallographic refinement of a protein model as a function of the resolution of the data. The data are assumed to be complete and the solvent content to be 50%.

Kallikreins can be roughly divided into two categories, the classical kallikreins (hKl, hK2, and hK3) and the new kallikreins. The new kallikreins appear to be unique in their three-dimensional structure and share some features with trypsins and other features with the classical kallikreins. Comparative protein models show that the pattern of hydrophobic side-chain packing in the protein core is nearly identical in all human kallikreins, and the observed differences occur within the solvent-exposed loop segments. 

Vorobjev YN, Almagro JC, Hermans J (1998) Discrimination between native and intentionally misfolded conformations of proteins ES/IS, a new method for calculating conformational free energy that uses both dynamics simulations with an explicit solvent and an implicit solvent continuum model, Proteins, 32 399-413... 

Microparticles, nanoparticles W/O/W solvent evaporation Model protein, tetanus toxoid PLA-PEG In rats Size-dependent mucosal uptake 66... 

Alanine was reinvestigated later, again pairing it with a molecule of water [143]. Quite a number of minima identified on that surface contained a CH- -O interaction, but unlike the earlier work which isolated the CH- - -O bond as the only H-bond present, these interactions were combined with a stronger conventional H-bond. This combination prevented an assessment of the energetic contribution of either one separate from the other. On the positive side, this work demonstrated that it was possible to submerge such systems in model solvents/proteins, and obtain meaningful results. 

Among the different available preparation techniques, direct formation of planar lipid bilayers from unilamellar vesicles is the most widespread method for obtaining solvent-free model membranes providing the required platform to study adsorption of proteins. 

T. J. P. Hubbard and T. L. Blundell, Protein Eng., 1, 159 (1987). Comparison of Solvent-Inaccessible Cores of Homologous Proteins Definition Useful for Protein Modeling. 

While molecular dynamics (MD) simulations have proven to be very powerful for studying numerous aspects of protein dynamics and structure [11-13], this technique cannot yet access the millisecond-to-second time-scales required for folding even a small protein. To address this timescale gap, one has to simplify the protein model by reducing the number of degrees of freedom. Such approaches assume that the basic physics could be reproduced in model systems that employ united atoms and effective solvent models. On the basis of recent work, it has become apparent that the crux of the solution to the protein folding problem does not lie in whether a reduced protein model is used, but rather in the development of... 

---