Conformations point mutations

Equations (5)-(8) assume that the energy functions (7 and Ub operate on the same conformation space i.e., A and B must have the same number N of degrees of freedom. In practice, this almost always implies that A and B have the same number of atoms or particles. Most biochemical changes of interest (e.g., point mutations of a protein) do not obey this requirement, but they can often be made to do so artificially through the use of dummy atoms (see below). 

Jl. Jaksch, M., Gerbitz, K. D., and Kilger, C., Screening for mitochondrial DNA (Mt DMA) point mutations using non radioactive single strand conformation polymorphism (SSCP) analysis. Clin. Biochem. 28, 503-509 (1995). 

Abstract The hallmark of chronic myelogenous leukemia (CML) is the expression of Bcr-Abl, a constitutively active form of the Abl tyrosine kinase. Imatinib, a 2-phenylamino-pyrimidine Bcr-Abl inhibitor developed by Novartis and marketed under the tradename of Gleevec (Glivec), is highly effective in treating CML patients with early stage disease. However, patients with advanced disease often become resistant to imatinib. The predominant form of this resistance is the development of mutations in the Bcr-Abl protein. These point mutations can be amino acid residues that make direct contact with imatinib or residues that do not allow Bcr-Abl to adopt the inactive conformation. Since imatinib can only bind to the inactive conformation of the protein, both types of mutations prevent this inhibitor from binding. Several approaches have been taken to identify additional... 

Figure 3 Decision scheme for the prediction of the conformation of a mutated residue. This scheme is based on two observations (1) A point mutation seldom leads to large alterations in the overall structure of the protein. The mutated residue adapts to the structure of the rest of the protein rather than the other way around. (2) Most residues sit lit the statistically preferred conformation, and when exceptions occur, they can normally be explaimi on the basis of hydrogen-bonding patterns. (Adapted from Ref. 37.)...

Later, in order to account for the effects of a point mutation on the activity of the p2-adrenergic receptor, Samama et al. [29] have proposed an extended version of the ternary complex model. In this model the receptor molecule exists in an equilibrium between the inactive R and the active R conformations. In the absence of ligand, the ability of the receptor to spontaneously convert from the inactive to the active conformation is determined by the isomerization constant, J. The active R conformation is the molecular species that enters into productive interaction with the G protein, described by the equilibrium constant M. The values of both J and M are dependent only on the receptor-G protein system, and are independent of the presence or absence of ligand. The ability of different ligands to perturb this equilibrium is gauged by the ligand-specific equilibrium constant (5, the... 

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