Prediction of folding rates and transition-state placement from native-state geometry

2003 ◽  
Vol 51 (1) ◽  
pp. 74-84 ◽  
Author(s):  
Cristian Micheletti
Keyword(s):  
Transition State ◽  
Native State ◽  
Folding Rates

Kinetic equivalence of the heat and cold structural transitions of λ 6–85

2005 ◽  
Vol 363 (1827) ◽  
pp. 565-573 ◽  
Author(s):  
Wei Y. Yang ◽  
Martin Gruebele
Keyword(s):  
Folding Kinetics ◽  
Native State ◽  
Temperature Changes ◽  
First Order ◽  
Hydrophobic Collapse ◽  
Folding Rates ◽  
Temperature Tuning ◽  
Pass Through ◽  
Denatured States ◽  
First Order Phase

Heat– and cold–denatured proteins are considered separate thermodynamic states because temperature tuning requires the protein to pass through two ‘soft’ first–order phase transitions. When both pressure and temperature changes are allowed, the heat– and cold–denatured states of proteins can be interconverted without going through the native state. This raises the question of whether these states are distinguished from one another by their folding kinetics. For the Tyr22Trp/Ala37Gly/Ala49Gly mutant of the 80 residue five–helix bundle protein λ 6−85 , we show that viscosity–corrected folding rates do not distinguish the cold– and heat–denatured states. We attribute this to a folding mechanism dominated by hydrophobic collapse. Our ‘temperature–symmetric’ approach offers an alternative to viscosity tuning with solvent additives in such cases.

Transition State Contact Orders Correlate with Protein Folding Rates

2005 ◽  
Vol 352 (3) ◽  
pp. 495-500 ◽  
Author(s):  
Emanuele Paci ◽  
Kresten Lindorff-Larsen ◽  
Christopher M. Dobson ◽  
Martin Karplus ◽  
Michele Vendruscolo
Keyword(s):  
Protein Folding ◽  
Transition State ◽  
Folding Rates

A Buried Ionizable Residue Destabilizes the Native State and the Transition State in the Folding of Monellin

Biochemistry ◽  
2012 ◽  
Vol 51 (45) ◽  
pp. 9058-9066 ◽  
Author(s):  
Nilesh Aghera ◽  
Ishita Dasgupta ◽  
Jayant B. Udgaonkar
Keyword(s):  
Transition State ◽  
Native State ◽  
Ionizable Residue

The unfolding transition state of ubiquitin with charged residues has higher energy than that with hydrophobic residues

2020 ◽  
Vol 22 (40) ◽  
pp. 23158-23168
Author(s):  
Tathagata Nandi ◽  
Amogh Desai ◽  
Sri Rama Koti Ainavarapu
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Transition State ◽  
State Structure ◽  
Native State ◽  
Hydrophobic Residues ◽  
Folding Pathways ◽  
Charged Residues

The native-state structure and folding pathways of a protein are encoded in its amino acid sequence.

scholarly journals Force Dependence of Proteins’ Transition State Position and the Bell–Evans Model

Nanomaterials ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3023
Author(s):  
Marc Rico-Pasto ◽  
Annamaria Zaltron ◽  
Felix Ritort
Keyword(s):  
Transition State ◽  
Single Molecule ◽  
High Energy ◽  
High Temporal Resolution ◽  
Native State ◽  
Force Extension ◽  
Single Molecule Force Spectroscopy ◽  
Large Hysteresis ◽  
Kinetic Rates ◽  
State Position

Single-molecule force spectroscopy has opened a new field of research in molecular biophysics and biochemistry. Pulling experiments on individual proteins permit us to monitor conformational transitions with high temporal resolution and measure their free energy landscape. The force–extension curves of single proteins often present large hysteresis, with unfolding forces that are higher than refolding ones. Therefore, the high energy of the transition state (TS) in these molecules precludes kinetic rates measurements in equilibrium hopping experiments. In irreversible pulling experiments, force-dependent kinetic rates measurements show a systematic discrepancy between the sum of the folding and unfolding TS distances derived by the kinetic Bell–Evans model and the full molecular extension predicted by elastic models. Here, we show that this discrepancy originates from the force-induced movement of TS. Specifically, we investigate the highly kinetically stable protein barnase, using pulling experiments and the Bell–Evans model to characterize the position of its kinetic barrier. Experimental results show that while the TS stays at a roughly constant distance relative to the native state, it shifts with force relative to the unfolded state. Interestingly, a conversion of the protein extension into amino acid units shows that the TS position follows the Leffler–Hammond postulate: the higher the force, the lower the number of unzipped amino acids relative to the native state. The results are compared with the quasi-reversible unfolding–folding of a short DNA hairpin.

scholarly journals DBFOLD: An efficient algorithm for computing folding pathways of complex proteins

2020 ◽  
Author(s):  
Amir Bitran ◽  
William M. Jacobs ◽  
Eugene Shakhnovich
Keyword(s):  
Monte Carlo ◽  
Protein Folding ◽  
Detailed Balance ◽  
Simulation Methods ◽  
Free Energies ◽  
Native State ◽  
Folding Rates ◽  
Computational Speed ◽  
Folding Pathways

AbstractAtomistic simulations can provide valuable, experimentally-verifiable insights into protein folding mechanisms, but existing ab initio simulation methods are restricted to only the smallest proteins due to severe computational speed limits. The folding of larger proteins has been studied using native-centric potential functions, but such models omit the potentially crucial role of non-native interactions.Here, we present an algorithm, entitled DBFOLD, which can predict folding pathways for a wide range of proteins while accounting for the effects of non-native contacts. In addition, DBFOLD can predict the relative rates of different transitions within a protein’s folding pathway. To accomplish this, rather than directly simulating folding, our method combines equilibrium Monte-Carlo simulations, which deploy enhanced sampling, with unfolding simulations at high temperatures. We show that under certain conditions, trajectories from these two types of simulations can be jointly analyzed to compute unknown folding rates from detailed balance. This requires inferring free energies from the equilibrium simulations, and extrapolating transition rates from the unfolding simulations to lower, physiologically-reasonable temperatures at which the native state is marginally stable. As a proof of principle, we show that our method can accurately predict folding pathways and Monte-Carlo rates for the well-characterized Streptococcal protein G. We then show that our method significantly reduces the amount of computation time required to compute the folding pathways of large, misfolding-prone proteins that lie beyond the reach of existing direct simulation methods. Our algorithm, which is available online, can generate detailed atomistic models of protein folding mechanisms while shedding light on the role of non-native intermediates which may crucially affect organismal fitness and are frequently implicated in disease.Author summaryMany proteins must adopt a specific structure in order to function. Computational simulations have been used to shed light on the mechanisms of protein folding, but unfortunately, realistic simulations can typically only be run for small proteins, due to severe limits in computational speed. Here, we present a method to solve this problem, whereby instead of directly simulating folding from an unfolded state, we run simulations that allow for computation of equilibrium folding free energies, alongside high temperature simulations to compute unfolding rates. From these quantities, folding rates can be computed using detailed balance. Importantly, our method can account for the effects of nonnative contacts which transiently form during folding and must be broken prior to adoption of the native state. Such contacts, which are often excluded from simple models of folding, may crucially affect real protein folding pathways and are often observed in folding intermediates implicated in disease.

A Dry Transition State More Compact Than the Native State Is Stabilized by Non-Native Interactions during the Unfolding of a Small Protein

Biochemistry ◽  
2017 ◽  
Vol 56 (29) ◽  
pp. 3699-3703 ◽  
Author(s):  
Sreemantee Sen ◽  
Rama Reddy Goluguri ◽  
Jayant B. Udgaonkar
Keyword(s):  
Transition State ◽  
Native State ◽  
Small Protein

Existence of DNA in yeast microbodies

1978 ◽  
Vol 36 (2) ◽  
pp. 232-233
Author(s):  
Masako Osumi ◽  
Misuzu Nagano ◽  
Hiroko Kazama
Keyword(s):  
Catalase Activity ◽  
Buoyant Density ◽  
Model System ◽  
Contour Length ◽  
Native State ◽  
Normal Alkane ◽  
Remarkable Increase ◽  
Dna Molecule ◽  
Mitochondrial Dnas

We have found that microbodies appeared profusely together with a remarkable increase in catalase activity in normal alkane-grown cells of hydrocarbon-utilizing Candida yeasts, and that the microbodies multiplied by division in these cells. These features of Candida yeasts seem to provide a useful model system for studies on the biogenesis of the microbody. Subsequently, we have succeeded in isolation of Candida microbodies in an apparently native state, as judged biochemically and morphologically. The presence of DNA in the purified microbody fraction thus obtained was proved by the diphenylamine method. DNA molecule of about 15 urn in contour length was released from an isolated microbody. The physicochemical analyses of the microbody DNA revealed that its buoyant density differed from nuclear and mitochondrial DNAs. All these results lead us to the possibility that there is a novel type of DNA in microbodies.

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