497 research outputs found
An Analytical Approach to the Protein Designability Problem
We present an analytical method for determining the designability of protein
structures. We apply our method to the case of two-dimensional lattice
structures, and give a systematic solution for the spectrum of any structure.
Using this spectrum, the designability of a structure can be estimated. We
outline a heirarchy of structures, from most to least designable, and show that
this heirarchy depends on the potential that is used.Comment: 16 pages 4 figure
A New Algorithm for Protein Design
We apply a new approach to the reverse protein folding problem. Our method
uses a minimization function in the design process which is different from the
energy function used for folding. For a lattice model, we show that this new
approach produces sequences that are likely to fold into desired structures.
Our method is a significant improvement over previous attempts which used the
energy function for designing sequences.Comment: 10 pages latex 2.09 no figures. Use uufiles to decod
Hiking in the energy landscape in sequence space: a bumpy road to good folders
With the help of a simple 20 letters, lattice model of heteropolymers, we
investigate the energy landscape in the space of designed good-folder
sequences. Low-energy sequences form clusters, interconnected via neutral
networks, in the space of sequences. Residues which play a key role in the
foldability of the chain and in the stability of the native state are highly
conserved, even among the chains belonging to different clusters. If, according
to the interaction matrix, some strong attractive interactions are almost
degenerate (i.e. they can be realized by more than one type of aminoacid
contacts) sequence clusters group into a few super-clusters. Sequences
belonging to different super-clusters are dissimilar, displaying very small
() similarity, and residues in key-sites are, as a rule, not
conserved. Similar behavior is observed in the analysis of real protein
sequences.Comment: 17 pages 5 figures Corrected typos added auxiliary informatio
Energetics of Protein-DNA Interactions
Protein-DNA interactions are vital for many processes in living cells,
especially transcriptional regulation and DNA modification. To further our
understanding of these important processes on the microscopic level, it is
necessary that theoretical models describe the macromolecular interaction
energetics accurately. While several methods have been proposed, there has not
been a careful comparison of how well the different methods are able to predict
biologically important quantities such as the correct DNA binding sequence,
total binding free energy, and free energy changes caused by DNA mutation. In
addition to carrying out the comparison, we present two important theoretical
models developed initially in protein folding that have not yet been tried on
protein-DNA interactions. In the process, we find that the results of these
knowledge-based potentials show a strong dependence on the interaction distance
and the derivation method. Finally, we present a knowledge-based potential that
gives comparable or superior results to the best of the other methods,
including the molecular mechanics force field AMBER99
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