Comparative modeling model building

Greer J. Comparative model-building of the mammalian serine proteinases. J Mol Biol 1981 153 1027-1042. 

The crystal structure has been revealed for some rodent kallikreins. The three-dimensional structure of a horse orthologue of the human hK3 has also been reported [28]. In contrast, hKl and hK6 are the only human kallikreins for which crystal structures have been determined [48-50]. Most of the discussion in this section is derived from comparative model building of the human kallikrein proteins. 

R. J. Read, G. D, Brayer, L. Jurasek, and M, N. G. James, Biochemistry, 26, 6570 (1984). Critical Evaluation of Comparative Model Building of Streptomyces grisus Trypsin,... 

J. Greer,/ Mol. Biol., 153, 1027 (1981). Comparative Model-Building of the Mammalian Serine Proteases. 

Table 2 WWW Locations of Modeling and Analysis Tools for Comparative Model Building...

All current comparative modeling methods consist of four sequential steps (Fig. 2) [5,6]. The first step is to identify the proteins with known 3D structures that are related to the target sequence. The second step is to align them with the target sequence and pick those known structures that will be used as templates. The third step is to build the model... 

This section briefly reviews prediction of the native structure of a protein from its sequence of amino acid residues alone. These methods can be contrasted to the threading methods for fold assignment [Section II.A] [39-47,147], which detect remote relationships between sequences and folds of known structure, and to comparative modeling methods discussed in this review, which build a complete all-atom 3D model based on a related known structure. The methods for ab initio prediction include those that focus on the broad physical principles of the folding process [148-152] and the methods that focus on predicting the actual native structures of specific proteins [44,153,154,240]. The former frequently rely on extremely simplified generic models of proteins, generally do not aim to predict native structures of specific proteins, and are not reviewed here. 

Therefore the author decided to create an artificial true mechanism, derive the kinetics from the mechanism without any simplification, and solve the resulting set of equations rigorously. This then can be used to generate artificial experimental results, which in turn can be evaluated for kinetic model building. Models, built from the artificial experiments, can then be compared with the prediction from the rigorous mathematical solution of the kinetics from the true mechanism. 

The result is the electron density map of the protein crystal. The final task for the crystallographer is to build the appropriate protein model, i. e., putting amino acid for amino acid into the electron density. Routinely the theoretical amplitudes and phases are calculated from the model and compared to the experimental data in order to check the correctness of model building. The positions of the protein backbone and the amino acid side chains are well defined by X-ray structures at a... 

Unfortunately, FfipFfop and HypoGen cannot process the large training sets of the size used for QSAR model building. The set of 29 most potent Cox2 inhibitors has been submitted to HipHop and the best of the resulting hypotheses has been qualitatively compared to the overlay-based QSAR model hypothesis. 

Model building in the computer is used to compare the influence of remote contacts on the stereochemistry and properties of P-1,2-, p-1,3-, and P-1,4-glucans, including their optical rotation behavior, and to explore the possibility of chain folding in cellulose, chltin, and xylan derivatives. 

The aim of correlation analysis is to compare one or more functions and to calculate their relationship with respect to a change of t (lag) in time or distance. In this way, memory effects within the time curve or between two curves can be revealed. Model building for the time series is easy if information concerning autocorrelation is available. 

This chapter addresses how silicon cell models can be used in biosimulation for systems biology. We first describe the process of model building, as well as its purpose and how it fits in systems biology. Then we compare the use of silicon cell models with the use of the less-detailed core models. We briefly discuss various simulation methods used to model phenomena involving diffusion and/or stochas-ticity as well as methods for model analysis. Finally we discuss balanced truncation as a method for model reduction. This method is illustrated by applying it to a silicon cell model of yeast glycolysis. 

To compare and evaluate different kinds of models created during the model development process graphical and statistical methods should be applied. A good description of the model building process can be found elsewhere [14]. 

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