Translation functions

Translational functions in eq. (100) cancel out because of the approximation adopted, the vibrational functions also cancel. The logarithm of the ratio of rotation functions possesses a constant value of —.246. The contribution of the exponential term is considerably higher and therefore determines the value of the disproportionation constant. Theoretical values of log K listed in Table X... 

Evans, W. E. Relling, M. V. (1999). Pharmacogenomics translating functional genomics into rational therapeutics. Science, 286,487-91. 

Plants are eukaryotic organisms whose post-translational functionalities empower protein synthesis capabilities, with the advantage of the economy of scale when cultivated at large scale. Therefore, the company s biomanufacturing is based in using plants as proteins manufacturers, since their capacity for folding proteins correctly at equivalent specific activities to those of native-sourced proteins. 

Evans WE, Relling MV. Pharmacogeno-mics Translating functional genomics into rational therapies. Science 1999 206 487-491 also see http // www.sciencemag. org/feature/data j 1044449.shl/. 

Evans WE, Reeling MV. Pharmacoge-nomics translating functional genomics... 

Evans, W.E. and M.V. Relling, "Pharmacogenomics Translating Functional Genomics into Rational Therapeutics," Science, 286, 487-491 (1999). 

Another possibility is to look at the packing of the top 10 solutions, because this can prove a very discriminating criterion. Even if the solution is well detached, it is still mandatory (and reassuring) to examine carefully the corresponding packing arrangement. This necessary (but not sufficient) condition can actually be implemented in the translation function using analytical expression... 

The need for automated protocols is apparent from the strategy adopted by AMoRe to circumvent the problem that the score of the rotation function (RF) is far from being perfect and does not always rank the solutions correctly (Navaza, 2001). Indeed, it is often observed that the true solution is not the top solution, with many false positives. Hence, AMoRe runs a translation function (TF) for each of, typically, the top 50 or 100 solutions of the rotation function. This is actually quite rapid as TF is based on FFT then, the first 10 solutions of each of these TF runs is in turn refined using a very effective implementation of rigid-body refinement (Navaza, 2001). 

If there is NCS in the crystal, all molecules of the asymmetric unit must be searched in turn every time a potential solution has been found, it is possible to use this information to increase the signal-to-noise ratio of the searches for the other molecules. But then, the combinatorics of testing the 50 top solutions of the rotation function and then the 10 top solutions of each associated translation function for rigid-body refinement cannot be done by hand as in the previous case, as soon as there is more than two molecules in the asymmetric unit. In NCS-MR, depending on the number of molecules present in the asymmetric unit, there are thousands of possibilities to be searched. Also, as one is searching with only a fraction of the asymmetric unit, the signal to be expected is intrinsically lower. 

As we mentioned already, the problem of the rotation function is its score, leading to a difficult energy landscape to be searched we can now describe another way to tackle this problem. Since the Translation Function score is much more sensitive, one might try to run a translation for every possible rotation angle, therefore exploring the 6D space exhaustively. The space to be searched in eule-rian angles depends on the space group of the crystal and can be found in Rao et al. (1980). It turns out that it is doable in most cases within reasonable cpu time with a normal workstation. 

Protocol 7.6 Full 6D search with the phased translation function ... 

Bentley, G. (1997) Phased translation function. Method Enzymol. 276, 611-619. 

Harada, Y., Lifchitz, A., Berthou, J., and JoUes, P. (1981) A translation function combining packing and diffraction information an apphcation to lysozyme (high-temperature form). Acta Crystallogr. A 37,398-406. 

Sheriff, S., Klei, H. E., and Davis, M. E. (1999) Implementation of a six-dimensional search using the AMoRe translation function for difficxilt molecxilar-replacement problems. J. Appl. Crystallogr. 32, 98-101. 

Fujinaga, M. and Read, R. J. (1987). Experiences with a new translation-function program. /. Appl. Cryst. 20,517-521. 

Cowtan, K. (1998). Modified phased translation functions and their application to molecntlar-fragment location. Acta Crystallogr. D 54,750-756. 

McCoy, A. J., et al. (2005). Likelihood enhanced fast translation functions. Acta Crystallogr. D 61,458 64. 

Vagin, A. A. and Isupoy M. N. (2001). Spherically averaged phased translation function and its apphcation to the search for molecules and fragments in electron-density maps. Acta Crystallogr. D 57,1451-1456. 

Evans, W.E. and Relling, M.V. (1999) Pharmacogenomics translating functional genomics into rational therapeutics. Science, 286, 487—4-91. Wijnen, P.A. et cd. (2007) Review article. The prevalence and clinical relevance of cytochrome P450 polymorphisms. Aliment. Pharmacol. Then, 26 (Suppl 2), 211-219. 

For the rotovibrational spectra of molecules interacting through purely isotropic forces, the Hamiltonian may be written as the sum of two independent terms. One term describes the rotational motion of the molecules, the other the translational motion of the pair. The total energy of the system is then equal to the sum of the rotovibrational and the translational energies. At the same time, the supermolecular wavefunctions are products of rotovibrational and translational functions. Let r designate the set of the rotovibrational quantum numbers and t the set of translational quantum numbers, the equation for yo may be written [314]... 

Synthetic chemists are uniquely situated to meet these challenges, as they are skilled in translating function into structure and structure into a viable if not practical plan of synthesis. 

Because ALBP is related to several proteins of known structure, molecular replacement is an attractive option for phasing. The choice of a phasing model is simple here just pick the one with the amino-acid sequence most similar to ALBP, which is myelin P2 protein. Solution of rotation and translation functions refers to the search for orientation and position of the phasing model (P2) in the unit cell of ALBP. The subsequent paper provides more details. 

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