Refining the program

The data base and the program on which we will base the following discussions are given in Table 6.1 and Table 6.2. Lines beginning with / are comments, the end of the comment is indicated by /. 

With the existing version of the PROLOG program the predicate hrf allows for retrieving the Rf values for the compounds in the data base. Backtracking supplies this information for other TLC systems. The same predicate used with the variable for the Rf value instantiated returns the names of compounds with Rf values within the range specified by the tolerance window. The predicate sep checks whether there is a TLC system that separates the two compounds specified. 

The three operations listed above are quite similar, they involve the correlation of compound names with Rf values, as performed by the predicate hrf. As arguments we will have the two lists, Clist and Rlist, the TLC system code and the tolerance level. Corresponding elements of the two lists will have to satisfy the relation hrf. We therefore check the relation hrf for the heads Cl and R1 of the respective lists and then recur on the tails Ctail and Rtail. The recurrence stops when either list is reduced to the empty list. Thus  

If a rather large value for Tol is specified, a flaw in the current program will become obvious. Sometimes, a given compound will match with more than one Rf value, and the same name will appear more than once in Clist. This can be corrected by adding a rule which states that a compound should be added to Clist only if it is not yet a member of Clist. This, however, presents a problem. As we process the lists by cutting away their heads, we have no direct access to the parts already processed. 

We can, however, concurrently with cutting down Clist by removing its head Cl build up another list C by adding Cl as the new head. Before joining Cl to the list C we make sure that Cl is not yet a member of this list. Initially, the list C is empty or uninstantiated. We now have 

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Step 11. At this point a computer program refines the atomic parameters of the atoms that were assigned labels. The atomic parameters consist of the three position parameters x,j, and for each atom. Also one or six atomic displacement parameters that describe how the atom is "smeared" (due to thermal motion or disorder) are refined for each atom. The atomic parameters are varied so that the calculated reflection intensities are made to be as nearly equal as possible to the observed intensities. During this process, estimated phase angles are obtained for all of the reflections whose intensities were measured. A new three-dimensional electron density map is calculated using these calculated phase angles and the observed intensities. There is less false detail in this map than in the first map. 

First, the structure should explain the data. Apart from the energy or target function value returned by the refinement program, this check can be performed with some independent programs (e.g., AQUA/PROCHECK-NMR [90], MOLMOL [91]). The analysis of the deviations from the restraints used in calculating the structures is very useful in the process of assigning the NOE peaks and refining the restraint list. As indicators of the quality of the final structure they are less powerful, because violations have been checked and probably removed. A recent statistical survey of the quality of NMR structures found weak correlations between deviations from NMR restraints and other indicators of structure quality [88]. 

The reaction flow-charts of Part Two, and indeed all chemical formulae which appear in this book, were generated by computer. The program used for these drawings was ChemDraw adapted for the Macintosh personal computer by Mr. Stewart Rubenstein of these Laboratories from the molecular graphics computer program developed by our group at Harvard in the 1960 s (E. J. Corey and W. T. Wipke, Science, 1969,166, 178-192) and subsequently refined. 

The structure was refined with the program RESTRAIN (35) using all data between 12.0 and 1.72 A. In the final cycles of refinement all the protein and solvent atoms were allowed to refine isotropically, but... 

Experiment with the program by varying EPS and K to refine the final runs. 

Schaumann T, Braun W, Wilthrich K. The program FANTOM for energy refinement of polypeptides and proteins using a Newton-Raphson minimizer in torsion angle space. Biopolymers 1990 29 679-694. 

Pattern 6.5, Recursive Refinement The ideas of refinement apply at all levels, from describing organizations and business processes to program code. This means that it can form the single consistent basis for traceability. 

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