Inverse folding problem

With the realization that there are only a limited number of stable folds and many unrelated sequences that have the same fold, biologically oriented computer scientists started to address what is called the inverse folding problem namely, which sequence patterns are compatible with a specific fold If this question can be answered, such patterns could be used to search through the genome sequence databases and extract those sequences that have a specific fold, such as the cx/p barrel or the immunoglobulin fold. 

A. Godzik, A. Kolinski, and J. Skolnick, Topology fingerprint approach to the inverse folding problem. J. Mol Biol 111, 221-23% (1992). 

The de novo protein design relies on understanding the relationship between the amino acid sequence of a protein and its three-dimensional struc-fMre.41 42.43,44,45,46 problem begins with a known protein three-dimensional structure and requires the determination of an amino acid sequence compatible with this structure. At the outset the problem was termed the inverse folding problem since protein design has intimate links to the well-known protein folding problem." ... 

How to design sequences tliat adopt a specified fold [9] This is tire inverse protein folding problem tliat is vital to the biotechnology industry. There are some proteins tliat do not spontaneously reach tire native confomiation. In tire cells tliese proteins fold witli tire assistance of helper molecules referred to as chaperonins. The chaperonin-mediated folding problem involves an understanding of tire interactions between proteins. 

A Godzik, A Kolinski, J Skolmck. Topology fingerprint approach to the inverse protein folding problem. J Mol Biol 227 227-238, 1992. 

The ultimate goal of protein engineering is to design an amino acid sequence that will fold into a protein with a predetermined structure and function. Paradoxically, this goal may be easier to achieve than its inverse, the solution of the folding problem. It seems to be simpler to start with a three-dimensional structure and find one of the numerous amino acid sequences that will fold into that structure than to start from an amino acid sequence and predict its three-dimensional structure. We will illustrate this by the design of a stable zinc finger domain that does not require stabilization by zinc. 

Inverse folding can be viewed as an optimization problem that can be treated with simple heuristics. This is what the RNAinverse program does for you. Input for the RNAinverse program consists of an RNA secondary structure (the target) in bracket notation (on the first line), optionally followed by a sequence to be used as the starting point of the optimization (otherwise a random start sequence is used). 

The Inverse Protein Folding Problem Protein Design and Structure Prediction in the Genomic Era... 

Molecular modeling is also used in protein engineering to modify specifically or randomly selected residues of a protein to change the substrate specificity or to try to find an amino acid sequence that will fold into a specific, preselected 3D shape (the inverse protein folding problem). An introduction to this topic has been written by van Gunsteren. xhe principles of modeling have also been used to design new enzymes with altered substrate specificity. - ... 

How to design sequenees that adopt a speeified fold [9] This is the inverse protein folding problem that is vital to the bioteehnology industry. There are some proteins that do not spontaneously reaeh the native eonformation. In the eells these proteins fold with the assistanee of helper moleeules referred to as ehaperonins. The ehaperonin-mediated folding problem involves an understanding of the interaetions between proteins. 

The rate constants and k represent rate constants for a surface reaction and have units m mol s and s respectively. The accelerative effects are about 10 -10 fold. They indicate that both reactants are bound at the surface layer of the micelle (surfactant-water interface) and the enhanced rates are caused by enhanced reactant concentration here and there are no other significant effects. Similar behavior is observed in an inverse micelle, where the water phase is now dispersed as micro-droplets in the organic phase. With this arrangement, it is possible to study anion interchange in the tetrahedral complexes C0CI4 or CoCl2(SCN)2 by temperature-jump. A dissociative mechanism is favored, but the interpretation is complicated by uncertainty in the nature of the species present in the water-surfactant boundary, a general problem in this medium. 

Using the structural coefficients in table 3.3 implies knowledge of the conditions of internal disorder of the various cations in the structure. In most cases (especially for pure components), this is not a problem. For instance, table 3.4 shows the decomposition into structural components of the acmite molecule, in which all Na+ is in Vlll-fold coordination with oxygen, Fe + is in Vl-fold coordination, and Si is in tetrahedral coordination. In some circumstances, however, the coordination states of the various elements are not known with sufficient precision, or, even worse, vary with T. A typical example is spinel (MgAl204), which, at T < 600 °C, has inversion X = 0.07 (i.e., 7% of the tetrahe-drally coordinated sites are occupied by Al +) and, at T = 1300 °C, has inversion X = 0.21 (21% of tetrahedral sites occupied by AF ). Clearly the calculation of... 

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