Related papers: Thoughts on the Proteins Native State
We study a large data set of protein structure ensembles of very diverse sizes determined by nuclear magnetic resonance. By examining the distance-dependent correlations in the displacement of residues pairs and conducting finite size…
Proteins have evolved through mutations, amino acid substitutions, since life appeared on Earth, some 109 years ago. The study of these phenomena has been of particular significance because of their impact on protein stability, function,…
Many protein systems fold in a two-state manner. Random models, however, rarely display two-state kinetics and thus such behavior should not be accepted as a default. To date, many theories for the prevalence of two-state kinetics have been…
It is a common belief that metamorphic proteins challenge the Anfinsen thermodynamic hypothesis (or dogma). Here we argue against this view aims to show that metamorphic proteins not just fulfill the Anfinsen dogma but also exhibit marginal…
The differing ability of polypeptide conformations to act as the native state of proteins has long been rationalized in terms of differing kinetic accessibility or thermodynamic stability. Building on the successful applications of physical…
The folding dynamics of small single-domain proteins is a current focus of simulations and experiments. Many of these proteins are 'two-state folders', i.e. proteins that fold rather directly from the denatured state to the native state,…
We argue that protein native state structures reside in a novel "phase" of matter which confers on proteins their many amazing characteristics. This phase arises from the common features of all globular proteins and is characterized by a…
We explore the possibility for the native state of a protein being inherently a multi-conformation state in an ab initio coarse-grained model. Based on the Wang-Landau algorithm, the complete free energy landscape for the designed sequence…
The prediction of the biologically active native conformation of a protein is one of the fundamental challenges of structural biology. This problem remains yet unsolved mainly due to three factors: the partial knowledge of the effective…
The primary aim of this work is to explore how proteins point mutations impact their marginal stability and, hence, their evolvability. With this purpose, we show that the use of four classic notions, namely, those from Leibniz & Kant…
We review and further develop an analytical model that describes how thermodynamic constraints on the stability of the native state influence protein evolution in a site-specific manner. To this end, we represent both protein sequences and…
These lectures will address two questions. Is there a simple variational principle underlying the existence of secondary motifs in the native state of proteins? Is there a general approach which can qualitatively capture the salient…
Globular proteins are expected to assume folds with fixed secondary structures, alpha-helices and beta-sheets. Fold-switching proteins challenge this expectation by remodeling their secondary and/or tertiary structures in response to…
We report here a new entropic mechanism of protein thermostability due to residual dynamics of rotamer isomerization in native state. All-atom simulations show that Lysines have much greater number of accessible rotamers than Arginines in…
The time evolution of the formation probability of native bonds has been studied for designed sequences which fold fast into the native conformation. From this analysis a clear hierarchy of bonds emerge a) local, fast forming highly stable…
By balancing the average energy gap with its typical change due to mutations for protein-like heteropolymers with M residues, we show that native states are unstable to mutations on a scale M* ~ (lambda/sigma_mu)^(1/zeta_s), where lambda is…
Neither of the two prevalent theories, namely thermodynamic stability and kinetic stability, provides a comprehensive understanding of protein folding. The thermodynamic theory is misleading because it assumes that free energy is the…
Evolutionally conserved quantity that specifies folding nuclei is pursued by a case study for a small protein (PDB code: 1ten). First it is demonstrated that the sequences of amino acids at folding nuclei are not conserved. Then 3D…
Use of a combination of statistical thermodynamics and the Gershgorin theorem enable us to guess, in the thermodynamic limit, a plausible value for the upper bound free-energy difference between native-like structures of monomeric globular…
It has been conjectured that evolution exerted pressure to preserve amino acids bearing thermodynamic, kinetic, and functional roles. In this letter we show that the physical requirement to maintain protein stability gives rise to a…