Difference proteins

Brooks, B. R., Janezic, D., Karplus, M. Harmonic Analysis of Large Systems I. Methodology. J. Comput. Chem. 16 (1995) 1522-1542 Janezic, D., Brooks, B. R. Harmonic Analysis of Large Systems II. Comparison of Different Protein Models. J. Comput. Chem. 16 (1995) 1543-1553 Janezic, D., Venable, R. M., Brooks, B. R. Harmonic Analysis of Large Systems. HI. Comparison with Molecular Dynamics. J. Comput. Chem. 16 (1995) 1554-1566... 

Ithough knowledge-based potentials are most popular, it is also possible to use other types potential function. Some of these are more firmly rooted in the fundamental physics of iteratomic interactions whereas others do not necessarily have any physical interpretation all but are able to discriminate the correct fold from decoy structures. These decoy ructures are generated so as to satisfy the basic principles of protein structure such as a ose-packed, hydrophobic core [Park and Levitt 1996]. The fold library is also clearly nportant in threading. For practical purposes the library should obviously not be too irge, but it should be as representative of the different protein folds as possible. To erive a fold database one would typically first use a relatively fast sequence comparison lethod in conjunction with cluster analysis to identify families of homologues, which are ssumed to have the same fold. A sequence identity threshold of about 30% is commonly... 

Human blood plasma contains over 700 different proteins (qv) (1). Some of these are used in the treatment of illness and injury and form a set of pharmaceutical products that have become essential to modem medicine (Table 1). Preparation of these products is commonly referred to as blood plasma fractionation, an activity often regarded as a branch of medical technology, but which is actually a process industry engaged in the manufacture of speciaUst biopharmaceutical products derived from a natural biological feedstock (see Pharmaceuticals). 

Cellular protein biosynthesis involves the following steps. One strand of double-stranded DNA serves as a template strand for the synthesis of a complementary single-stranded messenger ribonucleic acid (mRNA) in a process called transcription. This mRNA in turn serves as a template to direct the synthesis of the protein in a process called translation. The codons of the mRNA are read sequentially by transfer RNA (tRNA) molecules, which bind specifically to the mRNA via triplets of nucleotides that are complementary to the particular codon, called an anticodon. Protein synthesis occurs on a ribosome, a complex consisting of more than 50 different proteins and several stmctural RNA molecules, which moves along the mRNA and mediates the binding of the tRNA molecules and the formation of the nascent peptide chain. The tRNA molecule carries an activated form of the specific amino acid to the ribosome where it is added to the end of the growing peptide chain. There is at least one tRNA for each amino acid. 

Wool has a complex chemical stmcture, composed mainly of a large number of different proteins (87). It is amphoteric in character because of the presence of basic amino and acidic carboxyl groups in the side chains of some of the component amino acids. In an aqueous acidic dyebath, protonation of the amino and carboxyl groups results in a net positive charge on the fiber. 

The influx of Ca(Il) across the presynaptic membrane is essential for nerve signal transmission involving excitation by acetylcholine (26). Calcium is important in transducing regulatory signals across many membranes and is an important secondary messenger hormone. The increase in intracellular Ca(Il) levels can result from either active transport of Ca(Il) across the membrane via an import channel or by release of Ca(Il) from reticulum stores within the cell. More than 30 different proteins have been linked to regulation by the calcium complex with calmoduhn (27,28). 

High-speed hammer or pin mills result in some selective grinding. Such mills combined with air classification can produce fractions with controlled protein content. An example of such a combination is a Bauer hurricane hammer mill combined with the Alpine Mikroplex superfine classifier. Flour with different protein content is needed for... 

To overcome the limitations of the database search methods, conformational search methods were developed [95,96,109]. There are many such methods, exploiting different protein representations, objective function tenns, and optimization or enumeration algorithms. The search algorithms include the minimum perturbation method [97], molecular dynamics simulations [92,110,111], genetic algorithms [112], Monte Carlo and simulated annealing [113,114], multiple copy simultaneous search [115-117], self-consistent field optimization [118], and an enumeration based on the graph theory [119]. 

To gain the most predictive utility as well as conceptual understanding from the sequence and structure data available, careful statistical analysis will be required. The statistical methods needed must be robust to the variation in amounts and quality of data in different protein families and for structural features. They must be updatable as new data become available. And they should help us generate as much understanding of the determinants of protein sequence, structure, dynamics, and functional relationships as possible. 

Protein folding remains a problem because there are 20 different amino acids tbat can be combined into many more different proteins tban there are atoms in the known universe. In addition there is a vast number of ways in which similar structural domains can be generated in proteins by different amino acid sequences. By contrast, the structure of DNA, made up of only four different nucleotide building blocks that occur in two pairs, is relatively simple, regular, and predictable. 

Figure 2.8 Adjacent antiparallel P strands are joined by hairpin loops. Such loops are frequently short and do not have regular secondary structure. Nevertheless, many loop regions in different proteins have similar structures, (a) Histogram showing the frequency of hairpin loops of different lengths in 62 different proteins, (b) The two most frequently occurring two-residue hairpin loops Type I turn to the left and Type II turn to the right. Bonds within the hairpin loop are green, [(a) Adapted from B.L. Sibanda and J.M. Thornton, Nature 316 170-174, 1985.]...

Table 2.2 Amino acid sequences of calcium-binding EF motifs in three different proteins Pamalbumin VKKAFAI I DQDKSGFIEEDELKLFLQNF Calmodulin FKEAFSLFDKDGDGT I TTKELGTVMRSL Troponin-C LADCFR I FDKNADGF I D lEELGE I LRAT...

Several motifs usually combine to form compact globular structures, which are called domains. In this book we will use the term tertiary structure as a common term both for the way motifs are arranged into domain structures and for the way a single polypeptide chain folds into one or several domains. In all cases examined so far it has been found that if there is significant amino acid sequence homology in two domains in different proteins, these domains have similar tertiary structures. 

Domains are formed by different combinations of secondary structure elements and motifs. The a helices and p strands of the motifs are adjacent to each other in the three-dimensional structure and connected by loop regions. Sequentially adjacent motifs, or motifs that are formed from consecutive regions of the primary structure of a polypeptide chain, are usually close together in the three-dimensional structure (Figure 2.20). Thus to a first approximation a polypeptide chain can be considered as a sequential arrangement of these simple motifs. The number of such combinations found in proteins is limited, and some combinations seem to be structurally favored. Thus similar domain structures frequently occur in different proteins with different functions and with completely different amino acid sequences. 

The eight-stranded a/p-barrel stmcture is one of the largest and most regular of all domain stmctures. A minimum of about 200 residues are required to form this structure. It has been found in many different proteins, most of which are enzymes, with completely different amino acid sequences and... 

Leucine residues 2, 5, 7, 12, 20, and 24 of the motif are invariant in both type A and type B repeats of the ribonuclease inhibitor. An examination of more than 500 tandem repeats from 68 different proteins has shown that residues 20 and 24 can be other hydrophobic residues, whereas the remaining four leucine residues are present in all repeats. On the basis of the crystal structure of the ribonuclease inhibitor and the important structural role of these leucine residues, it has been possible to construct plausible structural models of several other proteins with leucine-rich motifs, such as the extracellular domains of the thyrotropin and gonadotropin receptors. 

The a/p-barrel structure is one of the largest and most regular of all domain structures, comprising about 250 amino acids. It has so far been found in more than 20 different proteins, with completely different amino acid sequences and different functions. They are all enzymes that are modeled on this common scaffold of eight parallel p strands surrounded by eight a helices. They all have their active sites in very similar positions, at the bottom of a funnel-shaped pocket created by the loops that connect the carboxy end of the p strands with the amino end of the a helices. The specific enzymatic activity is, in each case, determined by the lengths and amino acid sequences of these loop regions which do not contribute to the stability of the fold. 

Before protein molecules attain their native folded state they may expose hydrophobic patches to the solvent. Isolated purified proteins will aggregate during folding even at relatively low protein concentrations. Inside cells, where there are high concentrations of many different proteins, aggregation could therefore occur during the folding process. This is prevented by... 

The general transcription factor TFllD is believed to be the key link between specific transcription factors and the general preinitiation complex. However, the purification and molecular characterization of TFllD from higher eucaryotes have been hampered by its instability and heterogeneity. All preparations of TFllD contain the TATA box-binding protein in combination with a variety of different proteins called TBP-associated factors, TAFs. When the preinitiation complex has been assembled, strand separation of the DNA duplex occurs at the transcription start site, and RNA polymerase II is released from the promoter to initiate transcription. However, TFIID can remain bound to the core promoter and support rapid reinitiation of transcription by recruiting another molecule of RNA polymerase. 

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