Computer Assisted Modeling Contributions of Computational Approaches to Elucidating Macromolecular Structure and Function (1987) / Chapter Skim
Currently Skimming:
4 Secondary Structure of Proteins and Nucleic Acids
4 Secondary Structure of Proteins and Nucleic Acids
Pages 32-40
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 32... ...
Minor forms include the .3 ~ n ~nr1 ni Ah; 2 ~ ~ ~.~ a_ _ ~ r ~ ~ ~" ~l-ucl,ure~ are Iormea Irom hydrogen bonding between the backbone amides of extended polypeptide strands. Although such features are properly considered tertiary structure' they are often discussed as secondary structure.
|
From page 33... ...
However, this is not yet a definite method of predicting secondary structure in proteins because the energy differences among conformers are relatively small compared to the interactions between the peptide and the rest of the protein and because of neglect of the solvent entropy terms. Statistical methods began with the efforts of Chou and Fasman (1974)
|
From page 34... ...
More frequently, this procedure is used with other computational techniques for examining combinations of patterns that may lead to recognizable structural motifs in three · ~ c .lmenslons. The general method used to study these problems involves only a few basic stepse First, one or more techniques are used to make the first assignment of structural features to patterns in a sequence for example, hypothesized secondary structural elements associated with specific partial sequences.
|
From page 35... ...
Several examples have appeared recently where this approach has been successfully applied to pattern-based elucidation of structural features of proteins of known and unknown structure (Abarb~nel, 1984,1986; Cohen et at., 1986; Taylor and Thornton, 1983~. Current Status and future Prospects The assignment of each amino acid in a protein sequence to a particular secondary structure class has rarely been more than 70 percent accurate and is often worse.
|
From page 36... ...
They were designed to calculate secondary structure only to specify which bases are paired. The computerized procedure uses experimental thermodynamic data on double-strand formation in synthetic RNA oligonucleotides (Freier et al., 1986~.A dynamic programming algorithm considers all possible base pairs in the RNA a sequence of N nucleotides has N(N-1~/2 possible base pairs and calculates the free energies of the corresponding structures.
|
From page 37... ...
The extensive thermodynamic data needed for correct prediction of secondary structure will most likely come from computer interpolation and extrapolation of lirnitecl data measured on synthetic oligonucleotides in a few solvents. Once we understand better the forces and energies involved in the interactions of nucleotides with solvent, ions, and each other, it will become easier to calculate secondary structures for large RNA molecules.
|
From page 38... ...
Novel methods are needed for RNA that take into account either implicitly or explicitly: the long range electrostatic repulsion of phosphates shielded by counter ions; the detailed conformation of hairpin, bulge, and interior loops; the hydrogen bonding between IOODS and ~in~l~_~t.r:`ncl-A rim_ "ions (pseudo-knots) ; non-Watson-Crick base pairs and triple base interactions; and all the usual London van-der-Waals interactions, including solvent.
|
From page 39... ...
We need mathematical and dynamic structural models of how an RNA virus replicates, how reverse transcriptase copies the RNA into DNA, and how the RNA is packaged into its protein coat. With this knowledge, we will be much closer to finding ways to prevent or cure diseases caused by RNA viruses, which include colds, influenza, AIDS, and hepatitis.
|
From page 40... ...
Fundamental advances in understanding this catalytic activity require knowledge of the location and structure of the active site of RNA enzymes. Computer calculations in conjunction with mutation experiments may allow us to progress most rapidly.
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.