A decade and a half of protein intrinsic disorder: Biology still waits for physics
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Some of the recent advances in this exciting field of intrinsically disordered proteins are summarized and some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs are considered.Abstract:
The abundant existence of proteins and regions that possess specific functions without being uniquely folded into unique 3D structures has become accepted by a significant number of protein scientists. Sequences of these intrinsically disordered proteins (IDPs) and IDP regions (IDPRs) are characterized by a number of specific features, such as low overall hydrophobicity and high net charge which makes these proteins predictable. IDPs/IDPRs possess large hydrodynamic volumes, low contents of ordered secondary structure, and are characterized by high structural heterogeneity. They are very flexible, but some may undergo disorder to order transitions in the presence of natural ligands. The degree of these structural rearrangements varies over a very wide range. IDPs/IDPRs are tightly controlled under the normal conditions and have numerous specific functions that complement functions of ordered proteins and domains. When lacking proper control, they have multiple roles in pathogenesis of various human diseases. Gaining structural and functional information about these proteins is a challenge, since they do not typically “freeze” while their “pictures are taken.” However, despite or perhaps because of the experimental challenges, these fuzzy objects with fuzzy structures and fuzzy functions are among the most interesting targets for modern protein research. This review briefly summarizes some of the recent advances in this exciting field and considers some of the basic lessons learned from the analysis of physics, chemistry, and biology of IDPs.read more
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Journal ArticleDOI
Critical assessment of methods of protein structure prediction (CASP) — round x
TL;DR: The Critical Assessment of Structure Prediction (CASP) as discussed by the authors was the first attempt to assess the state-of-the-art in protein structure modeling, with a focus on three-dimensional contact information.
Book ChapterDOI
Intrinsically Disordered Proteins
TL;DR: This Sprenger Briefs volume is dedicated to IDPs and IDPRs and an attempt is made to compress a massive amount of knowledge and into a digest that aims to be of use to those wishing a fast entry into this promising field of structural biology.
Journal ArticleDOI
Intrinsically Disordered Proteins and Their “Mysterious” (Meta)Physics
TL;DR: With their exceptional spatio-temporal heterogeneity and high conformational flexibility, IDPs/IDPRs represent complex systems that act at the edge of chaos and are specifically tunable by various means.
Journal ArticleDOI
Relating sequence encoded information to form and function of intrinsically disordered proteins.
TL;DR: This work summarizes recent advances that connect information encoded in IDP sequences to their conformational properties and functions through a combination of atomistic simulations and biophysical measurements synthesized into a coherent framework using polymer physics theories.
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Biophysics of protein evolution and evolutionary protein biophysics
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TL;DR: To underscore the biophysical constraints on natural selection, effects of protein mutations are surveyed, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution.
References
More filters
Journal ArticleDOI
Collective dynamics of small-world networks
TL;DR: Simple models of networks that can be tuned through this middle ground: regular networks ‘rewired’ to introduce increasing amounts of disorder are explored, finding that these systems can be highly clustered, like regular lattices, yet have small characteristic path lengths, like random graphs.
Book
The Structure of Scientific Revolutions
TL;DR: The Structure of Scientific Revolutions as discussed by the authors is a seminal work in the history of science and philosophy of science, and it has been widely cited as a major source of inspiration for the present generation of scientists.
Journal ArticleDOI
Emergence of Scaling in Random Networks
TL;DR: A model based on these two ingredients reproduces the observed stationary scale-free distributions, which indicates that the development of large networks is governed by robust self-organizing phenomena that go beyond the particulars of the individual systems.
Journal ArticleDOI
p53 mutations in human cancers
TL;DR: The p53 mutational spectrum differs among cancers of the colon, lung, esophagus, breast, liver, brain, reticuloendothelial tissues, and hemopoietic tissues as mentioned in this paper.
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