C. Chothia, MRC Laboratory of Molecular Biology, Cambridge University
PROTEIN FAMILIES AND GENE DUPLICATIONS IN 19 GENOMES
E. Koonin, National Center for Biotechnology Information National Library of Medicine
National Institutes of Health
The title will be announced later
R. Russell, Bioinformatics, SmithKline Beecham Pharmaceuticals, United Kingdom
Predicting Function from Protein Structure Comparison
A. Gutin, Myriad Genetics Inc.
Multipoint genetic linkage analysis on large human pedigrees
I. Gelfand and A Kister, Rutgers University
What is common to highly non-homologous proteins with Immunoglobulin-like fold?
A.V. Finkelstein, Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow
Region, Russia
FOLDING NUCLEI IN 3D PROTEIN STRUCTURES
We present and analyze the results of several new approaches to the problem of finding the folding nucleus in a given 3D protein structure. Firstly, we show that the participation of residues in the hydrophobic core and the secondary structure of native protein has a rather modest correlation with the experimentally found F values characterizing the participation of residues in the folding nuclei. Then we try to find the nuclei (the folded parts of the transition states) as the free energy saddle point(s) on the network of the folding/unfolding pathways using the branch-and-bound technique and dynamic programming. We also attempted to estimate the F values (indicating participation of a residue in the transition state) from solving of kinetic equations for the network of protein folding/unfolding pathways. These approaches give a better correlation with experiment, and the estimated folding time is consistent with the experimentally observed rapid folding of small proteins.
Cyrus Chothia, Sarah A. Teichmann and Martin Madera, MRC Laboratory of Molecular Biology, Cambridge University
Protein Families and Gene Suplications in 19 Genomes
The major transitions in the evolution from prokaryotes to vertebrates involve large increases in protein repertoires. Duplications of pre-existing genes, their divergence and, in many cases, recombination have an important role in these increases. The overall extent of these duplications is of considerable interest but not known. It can not be calculated from simple all-against-all comparison of genome sequences because many protein families have members that have diverged beyond the point where such comparisons can detect relationships. Very distant relationships can be detected, however, if the structure and function of proteins are known and here we use this information to determine the protein families and gene duplication rates in the genomes of seventeen prokaryotes, Saccharomyces cerevisiae and Caenorhabditis elegans. For genome sequences homologous to proteins of known structure, the size of the average family is proportion to the size of the genome. In Mycoplasma genatalium 58% of these sequences have been produced by gene duplications and 96% in C. elegans.
E. Koonin, National Center for Biotechnology Information National Library of Medicine National Institutes of Health
The title will be announced later
R. Russell, Bioinformatics, SmithKline Beecham Pharmaceuticals, United Kingdom
Predicting Function from Protein Structure Comparison
High throughput structure determination will likely provide many protein three-dimensional structures in advance of a clear understanding of protein function. If a protein is of known structure, but of unknown function, then functional insights can come from comparison to other proteins of known structure. If a protein adopts a fold seen previously, then it is important to determine whether the similarity implies an evolutionary and/or obvious functional relationship (i.e. a remote homology). Even when this is not the case, certain folds show a tendency to bind ligands in a common location (a supersite) that may reflect physical rather than evolutionary constraints. Finally, if no overall similarity at the fold level is apparent, then local similarities at the main-chain or side-chain level can imply a functional similarity. For this talk, I will present examples of all types of similarity. For several previously described protein structures, I will present new functional insights gleaned by structure comparison.
A. Gutin, Myriad Genetics Inc. USA
Multipoint genetic linkage analysis on large human pedigrees
The problem of reconstruction of inheritance pattern in large human pedigrees using information from many genetic markers is very complex; the number of all possible inheritance states grows exponentially with the number of individuals in a pedigree and the number of genetic markers considered. There are algorithms providing computationally exact solutions in two limiting cases; when the number of markers is small (less than 5) or when a pedigree is small (less than 25 people). To solve the problem in general case we have developed a new Monte Carlo procedure based on blocked Gibbs sampling. This procedure provides good approximate solutions for pedigrees of up to 200 individuals with any reasonable number of markers.
I. Gelfand and A Kister, Rutgers University
What is common to highly non-homologous proteins with Immunoglobulin-like fold?
In this work we found a set residues, which would always be present in Ig-like molecules. This set of structurally-similar amino acids constitutes a necessary characteristics of Immunoglobulin fold. It serves as the "base" of a structure of an Ig-folded molecule.
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