5,030 research outputs found
Frustration in Biomolecules
Biomolecules are the prime information processing elements of living matter.
Most of these inanimate systems are polymers that compute their structures and
dynamics using as input seemingly random character strings of their sequence,
following which they coalesce and perform integrated cellular functions. In
large computational systems with a finite interaction-codes, the appearance of
conflicting goals is inevitable. Simple conflicting forces can lead to quite
complex structures and behaviors, leading to the concept of "frustration" in
condensed matter. We present here some basic ideas about frustration in
biomolecules and how the frustration concept leads to a better appreciation of
many aspects of the architecture of biomolecules, and how structure connects to
function. These ideas are simultaneously both seductively simple and perilously
subtle to grasp completely. The energy landscape theory of protein folding
provides a framework for quantifying frustration in large systems and has been
implemented at many levels of description. We first review the notion of
frustration from the areas of abstract logic and its uses in simple condensed
matter systems. We discuss then how the frustration concept applies
specifically to heteropolymers, testing folding landscape theory in computer
simulations of protein models and in experimentally accessible systems.
Studying the aspects of frustration averaged over many proteins provides ways
to infer energy functions useful for reliable structure prediction. We discuss
how frustration affects folding, how a large part of the biological functions
of proteins are related to subtle local frustration effects and how frustration
influences the appearance of metastable states, the nature of binding
processes, catalysis and allosteric transitions. We hope to illustrate how
Frustration is a fundamental concept in relating function to structural
biology.Comment: 97 pages, 30 figure
Detecting Repetitions and Periodicities in Proteins by Tiling the Structural Space
The notion of energy landscapes provides conceptual tools for understanding
the complexities of protein folding and function. Energy Landscape Theory
indicates that it is much easier to find sequences that satisfy the "Principle
of Minimal Frustration" when the folded structure is symmetric (Wolynes, P. G.
Symmetry and the Energy Landscapes of Biomolecules. Proc. Natl. Acad. Sci.
U.S.A. 1996, 93, 14249-14255). Similarly, repeats and structural mosaics may be
fundamentally related to landscapes with multiple embedded funnels. Here we
present analytical tools to detect and compare structural repetitions in
protein molecules. By an exhaustive analysis of the distribution of structural
repeats using a robust metric we define those portions of a protein molecule
that best describe the overall structure as a tessellation of basic units. The
patterns produced by such tessellations provide intuitive representations of
the repeating regions and their association towards higher order arrangements.
We find that some protein architectures can be described as nearly periodic,
while in others clear separations between repetitions exist. Since the method
is independent of amino acid sequence information we can identify structural
units that can be encoded by a variety of distinct amino acid sequences
Unified perspective on proteins: A physics approach
We study a physical system which, while devoid of the complexity one usually
associates with proteins, nevertheless displays a remarkable array of
protein-like properties. The constructive hypothesis that this striking
resemblance is not accidental leads not only to a unified framework for
understanding protein folding, amyloid formation and protein interactions but
also has implications for natural selection.Comment: 26 pages, 15 figures, to appear on Phys. Rev.
Exploring the correlation between the folding rates of proteins and the entanglement of their native states
The folding of a protein towards its native state is a rather complicated
process. However there are empirical evidences that the folding time correlates
with the contact order, a simple measure of the spatial organisation of the
native state of the protein. Contact order is related to the average length of
the main chain loops formed by amino acids which are in contact. Here we argue
that folding kinetics can be influenced also by the entanglement that loops may
undergo within the overall three dimensional protein structure. In order to
explore such possibility, we introduce a novel descriptor, which we call
"maximum intrachain contact entanglement". Specifically, we measure the maximum
Gaussian entanglement between any looped portion of a protein and any other
non-overlapping subchain of the same protein, which is easily computed by
discretized line integrals on the coordinates of the atoms. By
analyzing experimental data sets of two-state and multistate folders, we show
that also the new index is a good predictor of the folding rate. Moreover,
being only partially correlated with previous methods, it can be integrated
with them to yield more accurate predictions.Comment: 8 figures. v2: new titl
Single DNA conformations and biological function
From a nanoscience perspective, cellular processes and their reduced in vitro
imitations provide extraordinary examples for highly robust few or single
molecule reaction pathways. A prime example are biochemical reactions involving
DNA molecules, and the coupling of these reactions to the physical
conformations of DNA. In this review, we summarise recent results on the
following phenomena: We investigate the biophysical properties of DNA-looping
and the equilibrium configurations of DNA-knots, whose relevance to biological
processes are increasingly appreciated. We discuss how random DNA-looping may
be related to the efficiency of the target search process of proteins for their
specific binding site on the DNA molecule. And we dwell on the spontaneous
formation of intermittent DNA nanobubbles and their importance for biological
processes, such as transcription initiation. The physical properties of DNA may
indeed turn out to be particularly suitable for the use of DNA in nanosensing
applications.Comment: 53 pages, 45 figures. Slightly revised version of a review article,
that is going to appear in the J. Comput. Theoret. Nanoscience; some typos
correcte
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