Sequence-structure relation

G Vriend, C Sander, PFW Stouten. A novel search method for protein sequence-structure relations using property profiles. Protein Eng 7 23-29, 1994. 

The experimental results for these clusters are presented in Figures 5-10 and 5-11. The 4F.A(Ar)1 data show that the emission from the cluster/bare molecule systems changes dramatically as a function of vibrational energy in the cluster. At higher energies, only the 0° of the bare molecule is observed with a 12 cm"1 hot molecule sequence structure related to the ethyl group bend (toward and away... 

Formally, sequence-structure relations are considered as mappings from sequence space onto a discrete space of structures (for a review see [39]) ... 

Uncertainty in modeling lies in the fact that a three-dimensional model can either support a structural hypothesis or can be the result of modeling artifacts. Computer modeling is subject to imprecision in the low resolution data, subjectivity in the generation of three-dimensional models, and uncertainty in the formation of structural hypotheses. The theory of possibility, based on fuzzy logic, is used to classify structural hypotheses according to their likelihood to contain multiple-sequence data consistent conformations based upon the sequence-structure relation, R. 

In this article we present the constraint graph representation used by MC-SYM to transform structural data into three-dimensional models. Then, we discuss the sequence-structure relation and the theory of possibility to assign plausibility coefficients to each structural hypothesis. Finally, we discuss the application of this technique to the lead-activated riboz5one and indicate how modeling was used iteratively with experimentation to derive its active structure. 

Hie Sequence-Structure Relation. Structural hypotheses are derived from available structural data and are distinguished by their patterns of base pairing and stacking. For each structural hypothesis and sequence, a three-dimensional modeling simulation is performed, for instance using the MC-SYM program. In fact, any three-dimensional... 

Calculating Possibilities. Consider the sequence-structure relation in Figure 2. A uniform probability of is assigned to each sequence. Note that the uniform distribution is not a requirement of the mathematical model. It was assumed that all sequences could adopt the same conformation. The possibility for each structural hypothesis to contain the conformation was computed using Zadeh s theory of possibility. 

Consider X as the set containing all conformations generated by MC-SYM for all sequence variants. From the sequence-structure relation, R, the focal elements are... 

A. Identifying Known Protein Structures Related to the Target Sequence... 

The World Wide Web has transformed the way in which we obtain and analyze published information on proteins. What only a few years ago would take days or weeks and require the use of expensive computer workstations can now be achieved in a few minutes or hours using personal computers, both PCs and Macintosh, connected to the internet. The Web contains hundreds of sites of Interest to molecular biologists, many of which are listed in Pedro s BioMolecular Research Tools (http // www.fmi.ch/biology/research tools.html). Many sites provide free access to databases that make it very easy to obtain information on structurally related proteins, the amino acid sequences of homologous proteins, relevant literature references, medical information and metabolic pathways. This development has opened up new opportunities for even non-specialists to view and manipulate a structure of interest or to carry out amino-acid sequence comparisons, and one can now rapidly obtain an overview of a particular area of molecular biology. We shall here describe some Web sites that are of interest from a structural point of view. Updated links to these sites can be found in the Introduction to Protein Structure Web site (http // WWW.ProteinStructure.com/). 

The most intensively investigated dehydroxylation is probably the reaction of Mg(OH)2, though detailed results are also available for the hydroxides of certain other divalent cations. Several summaries of the mechanistic deductions obtained from such work, including literature sources, were presented at a conference at Dijon in 1974 [87]. The extensive literature concerned with the thermal analysis of hydroxides has been reviewed by Dollimore [79] who has also included the behaviour of oxides. Water elimination can be regarded as the first in a sequence of structurally related steps through which the hydroxide is converted into the thermally most stable oxide. 

It is apparent, from the above short survey, that kinetic studies have been restricted to the decomposition of a relatively few coordination compounds and some are largely qualitative or semi-quantitative in character. Estimations of thermal stabilities, or sometimes the relative stabilities within sequences of related salts, are often made for consideration within a wider context of the structures and/or properties of coordination compounds. However, it cannot be expected that the uncritical acceptance of such parameters as the decomposition temperature, the activation energy, and/or the reaction enthalpy will necessarily give information of fundamental significance. There is always uncertainty in the reliability of kinetic information obtained from non-isothermal measurements. Concepts derived from studies of homogeneous reactions of coordination compounds have often been transferred, sometimes without examination of possible implications, to the interpretation of heterogeneous behaviour. Important characteristic features of heterogeneous rate processes, such as the influence of defects and other types of imperfection, have not been accorded sufficient attention. 

A plethora of stoichiometries and structural types are found for the chalcogen compounds of the Group 5 metals. Phases approximating to the composition MX have the NiAs-type structure, whereas the MX2 compounds have layer structures related to M0S2, Cdl2, or CdCl2 types. Sometimes complex layer sequences occur in which the 6-coordinate metal atom is alternatively octahedral and trigonal prismatic. 

The determination of the amino acid sequences of the sarcoplasmic reticulum Ca -ATPase [42] and of the closely related Na, K -ATPase [43,44] have opened a new era in the analysis of ion transport mechanisms. Since 1985, several large families of structurally related ion transport enzymes were discovered [3,34,45-50] that are the products of different genes. Within each family several isoenzymes may be produced from a single gene-product by alternative splicing (Table I). 

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