4,935 research outputs found
Directionality in protein fold prediction
<p>Abstract</p> <p>Background</p> <p>Ever since the ground-breaking work of Anfinsen et al. in which a denatured protein was found to refold to its native state, it has been frequently stated by the protein fold prediction community that all the information required for protein folding lies in the amino acid sequence. Recent in vitro experiments and in silico computational studies, however, have shown that cotranslation may affect the folding pathway of some proteins, especially those of ancient folds. In this paper aspects of cotranslational folding have been incorporated into a protein structure prediction algorithm by adapting the Rosetta program to fold proteins as the nascent chain elongates. This makes it possible to conduct a pairwise comparison of folding accuracy, by comparing folds created sequentially from each end of the protein.</p> <p>Results</p> <p>A single main result emerged: in 94% of proteins analyzed, following the sense of translation, from N-terminus to C-terminus, produced better predictions than following the reverse sense of translation, from the C-terminus to N-terminus. Two secondary results emerged. First, this superiority of N-terminus to C-terminus folding was more marked for proteins showing stronger evidence of cotranslation and second, an algorithm following the sense of translation produced predictions comparable to, and occasionally better than, Rosetta.</p> <p>Conclusions</p> <p>There is a directionality effect in protein fold prediction. At present, prediction methods appear to be too noisy to take advantage of this effect; as techniques refine, it may be possible to draw benefit from a sequential approach to protein fold prediction.</p
High fidelity of RecA-catalyzed recombination: a watchdog of genetic diversity
Homologous recombination plays a key role in generating genetic diversity,
while maintaining protein functionality. The mechanisms by which RecA enables a
single-stranded segment of DNA to recognize a homologous tract within a whole
genome are poorly understood. The scale by which homology recognition takes
place is of a few tens of base pairs, after which the quest for homology is
over. To study the mechanism of homology recognition, RecA-promoted homologous
recombination between short DNA oligomers with different degrees of heterology
was studied in vitro, using fluorescence resonant energy transfer. RecA can
detect single mismatches at the initial stages of recombination, and the
efficiency of recombination is strongly dependent on the location and
distribution of mismatches. Mismatches near the 5' end of the incoming strand
have a minute effect, whereas mismatches near the 3' end hinder strand exchange
dramatically. There is a characteristic DNA length above which the sensitivity
to heterology decreases sharply. Experiments with competitor sequences with
varying degrees of homology yield information about the process of homology
search and synapse lifetime. The exquisite sensitivity to mismatches and the
directionality in the exchange process support a mechanism for homology
recognition that can be modeled as a kinetic proofreading cascade.Comment: http://www.weizmann.ac.il/complex/tlusty/papers/NuclAcidRes2006.pdf
http://nar.oxfordjournals.org/cgi/content/short/34/18/502
Toward a Database of Geometric Interrelationships of Protein Secondary Structure Elements for De Novo Protein Design, Prediction and Analysis
Computational methods of analyzing, simulating, and modeling proteins are essential towards understanding protein structure and its interactions. Computational methods are easier as not all protein structures can be determined experimentally due to the inherent difficultly of working with some proteins. In order to predict, design, analyze, simulate or model a protein, data from experimentally determined proteins such as those located in the repository of the Protein Data Bank (PDB) are essential. The assumption here is that we can use pieces of known proteins to piece together a new protein hence, de novo protein design. The analysis of the geometric relationships between secondary structure elements in proteins can be extremely useful to protein prediction, analysis, and de novo design. This thesis project involves creating a database of protein secondary structure elements and geometric information for rapid protein assembly, de novo protein design, prediction and analysis
The intrinsic load-resisting capacity of kinesin
Conventional kinesin is a homodimeric motor protein that is capable of
walking unidirectionally along a cytoskeletal filament. While previous
experiments indicated unyielding unidirectionality against an opposing load up
to the so-called stall force, recent experiments also observed limited
processive backwalking under superstall loads. This theoretical study seeks to
elucidate the molecular mechanical basis for kinesin's steps over the full
range of external loads that can possibly be applied to the dimer. We found
that kinesin's load-resisting capacity is largely determined by a synergic
ratchet-and-pawl mechanism inherent in the dimer. Load susceptibility of this
inner molecular mechanical mechanism underlies kinesin's response to various
levels of external loads. Computational implementation of the mechanism enabled
us to rationalize major trends observed experimentally in kinesin's stalemate
and consecutive back steps. The study also predicts several distinct features
of kinesin's load-affected motility, which are seemingly counterintuitive but
readily verifiable by future experiment.Comment: 44 pages, 6 figure
Recommended from our members
Anti-phage islands force their target phage to directly mediate island excision and spread.
Vibrio cholerae, the causative agent of the diarrheal disease cholera, is antagonized by the lytic phage ICP1 in the aquatic environment and in human hosts. Mobile genetic elements called PLEs (phage-inducible chromosomal island-like elements) protect V. cholerae from ICP1 infection and initiate their anti-phage response by excising from the chromosome. Here, we show that PLE 1 encodes a large serine recombinase, Int, that exploits an ICP1-specific protein as a recombination directionality factor (RDF) to excise PLE 1 in response to phage infection. We show that this phage-encoded protein is sufficient to direct Int-mediated recombination in vitro and that it is highly conserved in all sequenced ICP1 genomes. Our results uncover an aspect of the molecular specificity underlying the conflict between a single predatory phage and V. cholerae PLE and contribute to our understanding of long-term evolution between phage and their bacterial hosts
- …