Solvent space

Since then, refinement methods were considerably improved with the introduction of constrained least-squares minimization, which significantly reduces the number of variables and increases the ratio data/parameters. Even with these methods, water structure more remote from the protein surface tends to be blurred or is featureless, rendering the interpretation of the less well-defined regions in solvent space more ambiguous or impossible. 

It is possible to adopt a simplex strategy to explore the neighbourhood of a promising solvent. The score values are not continuous and it is therefore not possible to make reflections of the worst vertex in a strict geometrical sense. It is, however, possible to make a simplex search in an approximate way. In the exploration of the solvent space, there are two principal properties to consider. The simplex is therefore a triangle and will be defined by three solvent points in the score plot. Let one vertex correspond to the promising candidate, or to a hitherto known "useful" solvent. The other vertices are chosen not too far from the first one. Run the reaction in the three solvents selected and determine in which experiment the oucome is least favourable. Discard this point and run a new experiment in a... 

Energy map of solvent space near protein molecules. 

We have made the following approximate calculation to estimate protein-water interactions by a less cumbersome procedure it is assumed that the protein molecule has a unique fixed structure determined by x-ray crystallography and interactions are calculated between the protein and a single water molecule in the absence of other solvent molecules. Using this simple system, one may consider all positions and orientations of the single water molecule relative to the protein in a step-wise manner. We present here the result of this calculation for the crystal of bovine pancreatic trypsin inhibitor (BPTI). The calculated energy, mapped in three dimensions, is a highly informative description of the crystal s solvent space. 

Application to the BPTI Crystal. The system to be simulated consisted of the protein atoms of one BPTI molecule (5) and 140 water molecules. The required number of water molecules could be calculated both from the volume of the crystal for which protein-water energy is zero or negative (solvent space) (9) and from unit cell volume and density of protein and water. Protein-water interactions were calculated as in the first part of this article, protein-protein interactions as described elsewhere ( ). Interactions between water molecules were calculated using the ST2 model, introduced by Rahman and Stillinger in a molecular dynamics simulation of liquid water (11). 

The concentration of the final solution, of course, depends on the relative proportions of polymer and solvent. In Chapter 3 the solutions were assumed to be dilute, generally below 1% concentration, because this is required to obtain molecular weights. However, many solutions are used in the 10% to 50% concentration range. More concentrated systems are better described as plasticized polymers. Daoud and Jannink (11) and others divided polymer-solvent space into several regions, plotting the volume fraction of polymer, cp, vs the excluded volume parameter, v (see Figure 4.5). Each of these... 

Myoglobin, the chapter-opening molecule, has 153 amino acid residues in a single polypeptide chain. It has eight separate a-helical sections that fold back on one another, with the prosthetic heme group held in a cavity inside the polypeptide. Most of the polar residues are found on the outside of the protein so that they can interact with the water solvent. Spaces in the interior of the protein are filled with nonpolar amino acids. Myoglobin gives cardiac muscle its characteristic red color. 

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