Time-dependent communication between multiple amino acids during protein folding

Chong, Song; Ham, Sihyun

doi:10.1039/d0sc07025d

Cited by 7 publications

(20 citation statements)

References 34 publications

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“…1). A similar combination of small barriers and transitions requiring maximal cooperativity between amino acids was found for the folding of small proteins 45 . The fluctuation-driven character of the open-closed transition is also evident in nonequilibrium pulling simulations of Phe4 using dissipation-corrected targeted MD 46 .…”

Section: Discussionsupporting

confidence: 62%

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Cooperative protein allosteric transition mediated by a fluctuating transmission network

Post

Lickert

Diez

et al. 2021

Preprint

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Allosteric communication between distant protein sites represents a key mechanism of biomolecular regulation and signal transduction. Compared to other processes such as protein folding, however, the dynamical evolution of allosteric transitions is still not well understood. As example of allosteric coupling between distant protein regions, we consider the global open-closed motion of the two domains of T4 lysozyme, which is triggered by local motions in the hinge region. Combining extensive molecular dynamics simulations with machine learning of contact features, we identify a network of interresidue distances that move in a concerted manner. The cooperative process originates from a cogwheel-like motion of the hydrophobic core in the hinge region, which constitutes a flexible transmission network. Through rigid contacts and the protein backbone, the small local changes of the hydrophobic core are passed on to the distant terminal domains and lead to the emergence of a rare global conformational transition. As in an Ising-type model, the cooperativity of the allosteric transition can be explained via the interaction of local fluctuations.

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Section: Discussionsupporting

confidence: 62%

“…A similar combination of small barriers and transitions requiring maximal cooperativity between amino acids was found for the folding of small proteins. 48…”

Section: Discussionmentioning

confidence: 99%

Cooperative protein allosteric transition mediated by a fluctuating transmission network

Post

Lickert

Diez

et al. 2021

Preprint

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“…Such effects are found when ligands bind to various macromolecules, in particular to receptors, during signal transduction in cell or in the case of intercellular interactions. Although low-molecular-weight ligands do not take part in the processes of protein folding [ 32 , 33 , 34 ] and DNA melting, the latter are substantially cooperative. Thus, cooperativity significantly affects both intracellular and intercellular regulation of life processes [ 25 , 35 , 36 , 37 , 38 ].…”

Section: Statistical Entropy In Description Of Living Systems At the ...mentioning

confidence: 99%

The Use of the Statistical Entropy in Some New Approaches for the Description of Biosystems

Аристов

Buchelnikov

Nechipurenko

2022

Entropy

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Some problems of describing biological systems with the use of entropy as a measure of the complexity of these systems are considered. Entropy is studied both for the organism as a whole and for its parts down to the molecular level. Correlation of actions of various parts of the whole organism, intercellular interactions and control, as well as cooperativity on the microlevel lead to a more complex structure and lower statistical entropy. For a multicellular organism, entropy is much lower than entropy for the same mass of a colony of unicellular organisms. Cooperativity always reduces the entropy of the system; a simple example of ligand binding to a macromolecule carrying two reaction centers shows how entropy is consistent with the ambiguity of the result in the Bernoulli test scheme. Particular attention is paid to the qualitative and quantitative relationship between the entropy of the system and the cooperativity of ligand binding to macromolecules. A kinetic model of metabolism. corresponding to Schrödinger’s concept of the maintenance biosystems by “negentropy feeding”, is proposed. This model allows calculating the nonequilibrium local entropy and comparing it with the local equilibrium entropy inherent in non-living matter.

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“…χ ij; kl t ð Þ for all the systems using their respective transition paths. 27 The results for the villin and the WW domain are shown as the orange curves in Figure 2B, E. The function χ(t) quantifies the cooperative formation between (i, j) amino acid contact and (k, l) amino acid contact: χ(t) = 0 when these contacts are formed independently, whereas χ(t) > 0 if these contacts are formed cooperatively.…”

Section: Dynamic Cooperativity In Protein Foldingmentioning

confidence: 99%

“…19,20,25,26 In particular, we have demonstrated that simultaneous formation of multiple amino acid contacts is a distinguishing characteristic unique to the folding transition path and that the folding transition state can be identified as the state in which the amino acid correlation is maximal. 27 This was done by analyzing multipoint time correlation function that measures time-dependent cooperativity, termed dynamic cooperativity, between amino acid contact formations. Importantly, the analysis of dynamic cooperativity can be performed solely from the folding transition paths of a single protein, that is, without introducing any mutations.…”

Section: Introductionmentioning

confidence: 99%

Evolutionary conservation of amino acids contributing to the protein folding transition state

Chong

Ham

2022

J Comput Chem

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The question of whether amino acids critical to protein folding kinetics are evolutionarily conserved has been investigated intensively in the past, but no consensus has yet been reached. Recently, we have demonstrated that the transition state, dictating folding kinetics, is characterized as the state of maximum dynamic cooperativity, i.e., the state of maximum correlations between amino acid contact formations. Here, we investigate the evolutionary conservation of those amino acids contributing significantly to the dynamic cooperativity. We find a strong indication of a new kind of relationship—necessary but not sufficient causality—between the evolutionary conservation and the dynamic cooperativity: larger contributions to the dynamic cooperativity arise from more conserved residues, but not vice versa. This holds for all the protein systems for which long folding simulation trajectories are available. To our knowledge, this is the first systematic demonstration of any kind of evolutionary conservation of amino acids relevant to folding kinetics.

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Time-dependent communication between multiple amino acids during protein folding

Abstract: Cooperativity is considered to be a key organizing principle behind biomolecular assembly, recognition and folding. However, it has remained very challenging to quantitatively characterize how cooperative processes occur on a...

Cited by 7 publications

References 34 publications

Cooperative protein allosteric transition mediated by a fluctuating transmission network

Cooperative protein allosteric transition mediated by a fluctuating transmission network

The Use of the Statistical Entropy in Some New Approaches for the Description of Biosystems

Evolutionary conservation of amino acids contributing to the protein folding transition state

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