Experimental structure

Approaches of de novo predictions, which try to calculate how the structural elements are folded into the 3D-stmcture (tertiary structure) of complete proteins are nowadays far away from reliable large-scale applications. On the other, hand this topic is under strong development indicated by recent successful results at the contest for structural prediction methods CASP4. With the fast growing number of experimentally solved 3D-stmctures of protein and new promising approaches like threading tools combined with experimental structural constraints, one can expect more reliable de novo predictions for 3D-protein structures in the future. 

The strongest verification for a 3D-protein model comes from the experimental 3D-structure. This is the objective of the Critical Assessment of Techniques for Protein Structure Prediction, CASP ( http //predic tioncenter.org), where the structural models are made in advance of the experimental structure of a particular protein. 

We have already thoroughly discussed the structural results of Vincent and Radom s ab initio investigation in Section 4.3. Most of their calculated parameters are in very good agreement with experimental structural data for the benzenediazo-... 

Table 7. B3LYP/SDD optimized and experimental structural parameters (in parentheses) for Et3Al—E(Tms)3 adducts (pm, °)...

Very similar values were calculated at the MP2(full)/6-31G level [48] and at the MP2/6-311++G level [34]. No experimental structure determination has been reported for tetrasulfane. 

Crystal structures of the NS5B polymerase alone and in complexes with nucleotide substrates have been solved and applied to discovery programs (Ago et al. 1999 Bressanelli et al. 2002 Bressanelli et al. 1999 Lesburg et al. 1999 O Farrell et al. 2003). From these studies, HCV polymerase reveals a three-dimensional structure that resembles aright hand with characteristic fingers, palm, and thumb domain, similar to the architectures of the RNA polymerases of other viruses. However, none of these experimental structures contained the ternary initiation complex with nu-cleotide/primer/template, as obtained with HIV RT. Accordingly, HCV initiation models have been built using data from other viral systems in efforts to explain SAR (Kozlov et al. 2006 Yan et al. 2007). 

Table 1.1 Optimized geometries at MP2 level and selected experimental structural parameters for [M2(NHCHNH)2] [8].

Very often, it is unknown which conformahon of a flexible molecule is needed. For example, in drug design, we hunt often for the so-called bioachve conformation, which is the molecule in its receptor-bound state. In this case, any other experimental structure of the isolated molecule - in vacuum, in soluhon or in crystal - can be the wrong choice. 

Often, one needs to compare different 3D structures or conformations of a molecule. That is done internally by the 3D stmcture generation program to weed out too similar conformations of fragments. Another aspect is the need of the computational chemist to compare different generated or experimental structures. A well-established measure is the so-called root mean square (RMS) value of all atom-atom distances between two 3D structures. The RMS value needed here is a minimum value achieved by superimposing the two 3D structures optimally. Before calculating the RMS, the sum of interatomic distances is minimized by optimizing the superimposition in 3D. 

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