Protein structure similarity/overlap

This chapter focuses on the application of molecular modeling to calculate, manipulate, and predict protein structures and functions. Concepts of structure similarity/ overlap, homology modeling, and molecular docking, which are special concerns of protein biochemists, are considered. Approaches to protein modeling by the use of two programs (Swiss-Pdb Viewer and KineMage) and two online servers (B and CE) are described. 

NMR structure determination of large membrane proteins is hampered by broad spectral lines, overlap, and ambiguity of signal assignment. Chemical shift and NOE assignment can be facilitated by amino acid-selective isotope labeling in a cell-free protein synthesis system. Researchers report the cell-free synthesis of subunits a and c of the proton channel of Escherichia coli ATP synthase in a solution form in a mixture of phosphatidylcholine derivatives. In comparison, subunit a was purified from the cell-free system and from the bacterial cell membranes. NMR speetra of both preparations were similar, indicating that the procedure for cell-free synthesis produces protein structurally similar to that prepared from the cell membranes. 

Aldose reductase (ALR2 EC 1.1.1.21) is an 36 kDa enzyme that catalyzes the reduction of a wide range of carbonyl-containing compounds to their corresponding alcohols. It is a member of an extensive aldo-keto oxidoreductase enzyme family, a collection of structurally similar proteins expressed in both animals and plants. Most members of the enzyme family possess similarities in molecular mass, pH optimum, coenzyme dependence, and demonstrate overlapping specificity for many substrates and inhibitors. 

B. S. Kendrick, A. Dong, S. D. Allison, M. C. Manning, and J. F. Carpenter, Quantitation of the area of overlap between second-derivative amide 1 infrared spectra to determine structural similarity of a protein in different states, J. Pharm. Sci. 7 5.155-158(1996). 

With protein structures, we can observe similarities in topology or even in structural details. Comparison of protein structures can reveal distant evolutionary relationships that would not be detected by sequence aligmnent alone. Comparing and overlapping two protein stractures quantitatively remain an active area of development in structural biochemistry. Methods for protein comparison generally rely on a fast full search of the protein structure database. 

TABLE 16.11 Online servers for protein structure alignment, similarity/overlap... 

Energy gaps of individual energy terms have also been examined [see Eqs. (1) and (2)]. Unless explicitly noted, all results presented below were performed without energy cutoffs that is, all possible non-bonded interactions are included in the total energy. The structural similarity between two protein conformations is expressed as a root mean square deviation (RMSD) between the best overlap of the alpha-carbon (Co) atoms of the two conformations. 

Separation of PHASCL and PHAMCL into two separate granules within the same cell often seems to occur if two different PHA synthases with non-overlapping substrate ranges are present in the cell. Obviously, each type of PHA synthase participates separately in the initiation of micelle formation of nascent PHA granules, because only PHA molecules of similar structure, which remain bound to the PHA synthase protein, can contribute to the formation of a micelle. When the granules become larger, further PHA synthase molecules can only bind to the surface of the granules if they represent the same type of PHA synthase. 

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