Model building mutations

As shown in Table 1, the trend in CYP homology model building is clearly toward a multi-integrated approach using multiple sequence alignments (multiple), structural alignments in combination with mutational, spectroscopic and enzyme kinetic experimental data and new or available pharmacophore models,... 

Is easy id predict the structure of a point mutant. They also determined a set of simple rules that can be used to predict the structure of a mutated residue given the structure of the wH4 ypc protein. These rules are described in Figure 3. It is to be expected—although it is not yet proven—that this simple scheme can be extrapolated to model building by homology in cases of high homology. 

For peptides and nucleic acids, the system should provide rapid generation of a model from sequence data in any of the commonly observed conformations (e.g., a-helix, /J-sheet, /2-turn, B-DNA, Z-DNA). For peptides, it should be possible to make insertions or deletions in the sequence easily and to mutate side chains for homology model-building applications, where the sequence of the unknown structure is mapped onto the three-dimensional structure of a sequentially homologous protein whose structure has previously been determined by X-ray crystallography. 

T4 lysozyme has two such cavities in the hydrophobic core of its a helical domain. From a careful analysis of the side chains that form the walls of the cavities and from building models of different possible mutations, it was found that the best mutations to make would be Leu 133-Phe for one cavity and Ala 129-Val for the other. These specific mutants were chosen because the new side chains were hydrophobic and large enough to fill the cavities without making too close contacts with surrounding atoms. 

If the sequence of a protein has more than 90% identity to a protein with known experimental 3D-stmcture, then it is an optimal case to build a homologous structural model based on that structural template. The margins of error for the model and for the experimental method are in similar ranges. The different amino acids have to be mutated virtually. The conformations of the new side chains can be derived either from residues of structurally characterized amino acids in a similar spatial environment or from side chain rotamer libraries for each amino acid type which are stored for different structural environments like beta-strands or alpha-helices. 

The biopolymer modeling of HyperChem includes Building polynucleotides, polypeptides and polysaccharides, Amino acid sequence (fasta format) editing, Mutations, Overlapping by RMS fit, and Merging structures. To facilitate manipulation of protein structures, there is often a need to display the protein backbone only as follows. 

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