Protein structure loop conformation

Step 1 A short conventional MD simulation (typically extending over a few lOOps) is performed to generate an ensemble of protein structures x 6 71 (each described by N atomic positions), which characterizes the initial conformational substate. The 2-dimensional sketch in Fig. 9 shows such an ensemble as a cloud of dots, each dot x representing one snapshot of the protein. 

There are two main classes of loop modeling methods (1) the database search approaches, where a segment that fits on the anchor core regions is found in a database of all known protein structures [62,94], and (2) the conformational search approaches [95-97]. There are also methods that combine these two approaches [92,98,99]. 

RNA structures, compared to the helical motifs that dominate DNA, are quite diverse, assuming various loop conformations in addition to helical structures. This diversity allows RNA molecules to assume a wide variety of tertiary structures with many biological functions beyond the storage and propagation of the genetic code. Examples include transfer RNA, which is involved in the translation of mRNA into proteins, the RNA components of ribosomes, the translation machinery, and catalytic RNA molecules. In addition, it is now known that secondary and tertiary elements of mRNA can act to regulate the translation of its own primary sequence. Such diversity makes RNA a prime area for the study of structure-function relationships to which computational approaches can make a significant contribution. 

Another example of a quantal repeat—but with considerable variation in sequence—is seen in the keratin-associated proteins (KAPs). In sheep, these display pentapeptide and decapeptide consensus repeats of the form G—G—Q—P—S/T and C-C-Q/R—P—S/T—C/S/T—C—Q—P/T—S, respectively (Parry et al., 1979). Some of the positions, as indicated by the presence of a consensus sequence, contain residues that occur much more frequently than others, but the absolute conservation of a residue in any position is not observed. The decapeptide consists of a pair of five-residue repeats closely related, but different to that displayed by the pentapeptide. Although the repeats have an undetermined structure, the similarity of the repeat to a sequence in snake neurotoxin suggests that the pentapeptides will adopt a closed loop conformation stabilized by a disulphide bond between cysteine residues four apart (Fig. 5 Fraser et al., 1988 Parry et al, 1979). Relative freedom of rotation about the single bond connecting disulphide-bonded knots would give rise to the concept of a linear array of knots that can fold up to form a variety of tertiary structures. The KAPS display imperfect disulphide stabilization of knots and have interacting... 

The first step, as alluded to above, is the development of possible loop conformations which connect the regions of secondary structure The loops which do not fit into the well-defined category of a-helices or (1-sheets have been fairly well characterized using the data base of proteins for which the three-dimensional structure is known [15,16], The identification of specific loop conformations provides insight into the possible orientations, or at least provides limitations on the possible orientations, of the various secondary structural elements. The second step is then analysis of the array of amino acids within the secondary structural elements with attention to the environment in which the amino acids would be found. It is clear that a cluster of hydrophobic amino acids would not likely be projecting into the aqueous solution, and more likely projecting into the core of the protein. This analysis provides additional restrictions to the number of possible arrangements in which the secondary structural elements may be found. 

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