scholarly journals Distinguishing Biomolecular Pathways and Metastable States

2019 ◽  
Author(s):  
Antonio Bento Oliveira Junior ◽  
Huan Yang ◽  
Paul Charles Whitford ◽  
Vitor Barbanti Pereira Leite
Keyword(s):  
Phase Space ◽  
Conformational Changes ◽  
Energy Landscape ◽  
Protein A ◽  
Elongation Factor ◽  
Two Dimensions ◽  
Visualization Method ◽  
Kinetic Information ◽  
Dimensional Phase Space ◽  
Distinct Features

Protein folding occurs in a high dimensional phase space, and the representation of the associated energy landscape is non-trivial. A widely applied approach to studying folding landscapes is to describe the dynamics along a small number of reaction coordinates. However, other strategies involve more elaborate analysis of the complex phase space. There have been many attempts to obtain a more detailed representation of all available conformations for a given system. In this work, we address this problem using a metric based on internal distances between amino acids to describe the differences between any two conformations. Using an effective projection method, we are able to go beyond the usual one-dimensional representation and thus visualize landscapes in two dimensions. We refer to this method as Energy Landscape Visualization Method (ELViM). We have applied this methodology using Cα structure-based model (SBM) to study the folding of two well-known proteins: SH3 domain and Protein-A. Our visualization method yields a detailed description of the folding process, making possible the identification of transition state regions, and establishing the paths that lead to the native state. For SH3, we have analyzed structural differences in the distribution of folding routes. The competition between the native and mirror structures in protein A is discussed. Finally the method is applied to discuss the conformational changes of the Elongation Factor Thermally unstable (EF-Tu) and its transition states. Distinct features of the ELViM are that it does not require or assume an existence of a reaction coordinate, and it does not require kinetic information regarding the investigated system.

scholarly journals Distinguishing Biomolecular Pathways and Metastable States

2019 ◽  
Author(s):  
Antonio Bento Oliveira Junior ◽  
Huan Yang ◽  
Paul Charles Whitford ◽  
Vitor Barbanti Pereira Leite
Keyword(s):  
Phase Space ◽  
Conformational Changes ◽  
Energy Landscape ◽  
Protein A ◽  
Elongation Factor ◽  
Two Dimensions ◽  
Visualization Method ◽  
Kinetic Information ◽  
Dimensional Phase Space ◽  
Distinct Features

Protein folding occurs in a high dimensional phase space, and the representation of the associated energy landscape is non-trivial. A widely applied approach to studying folding landscapes is to describe the dynamics along a small number of reaction coordinates. However, other strategies involve more elaborate analysis of the complex phase space. There have been many attempts to obtain a more detailed representation of all available conformations for a given system. In this work, we address this problem using a metric based on internal distances between amino acids to describe the differences between any two conformations. Using an effective projection method, we are able to go beyond the usual one-dimensional representation and thus visualize landscapes in two dimensions. We refer to this method as Energy Landscape Visualization Method (ELViM). We have applied this methodology using Cα structure-based model (SBM) to study the folding of two well-known proteins: SH3 domain and Protein-A. Our visualization method yields a detailed description of the folding process, making possible the identification of transition state regions, and establishing the paths that lead to the native state. For SH3, we have analyzed structural differences in the distribution of folding routes. The competition between the native and mirror structures in protein A is discussed. Finally the method is applied to discuss the conformational changes of the Elongation Factor Thermally unstable (EF-Tu) and its transition states. Distinct features of the ELViM are that it does not require or assume an existence of a reaction coordinate, and it does not require kinetic information regarding the investigated system.

scholarly journals Structural basis of human transcription–DNA repair coupling

Nature ◽  
2021 ◽  
Vol 598 (7880) ◽  
pp. 368-372
Author(s):  
Goran Kokic ◽  
Felix R. Wagner ◽  
Aleksandar Chernev ◽  
Henning Urlaub ◽  
Patrick Cramer
Keyword(s):  
Dna Repair ◽  
Rna Polymerase Ii ◽  
Conformational Changes ◽  
Protein A ◽  
Elongation Factor ◽  
Dna Lesions ◽  
Structural Basis ◽  
Elongation Complex ◽  
Pol Ii ◽  
Dna Lesion

AbstractTranscription-coupled DNA repair removes bulky DNA lesions from the genome1,2 and protects cells against ultraviolet (UV) irradiation3. Transcription-coupled DNA repair begins when RNA polymerase II (Pol II) stalls at a DNA lesion and recruits the Cockayne syndrome protein CSB, the E3 ubiquitin ligase, CRL4CSA and UV-stimulated scaffold protein A (UVSSA)3. Here we provide five high-resolution structures of Pol II transcription complexes containing human transcription-coupled DNA repair factors and the elongation factors PAF1 complex (PAF) and SPT6. Together with biochemical and published3,4 data, the structures provide a model for transcription–repair coupling. Stalling of Pol II at a DNA lesion triggers replacement of the elongation factor DSIF by CSB, which binds to PAF and moves upstream DNA to SPT6. The resulting elongation complex, ECTCR, uses the CSA-stimulated translocase activity of CSB to pull on upstream DNA and push Pol II forward. If the lesion cannot be bypassed, CRL4CSA spans over the Pol II clamp and ubiquitylates the RPB1 residue K1268, enabling recruitment of TFIIH to UVSSA and DNA repair. Conformational changes in CRL4CSA lead to ubiquitylation of CSB and to release of transcription-coupled DNA repair factors before transcription may continue over repaired DNA.

A one-dimensional self-gravitating stellar gas

1966 ◽  
Vol 25 ◽  
pp. 46-48 ◽  
Author(s):  
M. Lecar
Keyword(s):  
Gravitational Field ◽  
Phase Space ◽  
Motion Picture ◽  
Space Distribution ◽  
Two Dimensional ◽  
One Dimensional ◽  
Phase Space Distribution ◽  
Dimensional Phase Space ◽  
The Mean

“Dynamical mixing”, i.e. relaxation of a stellar phase space distribution through interaction with the mean gravitational field, is numerically investigated for a one-dimensional self-gravitating stellar gas. Qualitative results are presented in the form of a motion picture of the flow of phase points (representing homogeneous slabs of stars) in two-dimensional phase space.

scholarly journals Geometric particle-in-cell methods for the Vlasov–Maxwell equations with spin effects

2021 ◽  
Vol 87 (3) ◽  
Author(s):  
Nicolas Crouseilles ◽  
Paul-Antoine Hervieux ◽  
Yingzhe Li ◽  
Giovanni Manfredi ◽  
Yajuan Sun
Keyword(s):  
Phase Space ◽  
Maxwell Equations ◽  
Stimulated Raman Scattering ◽  
Extended Phase ◽  
Five Dimensions ◽  
Particle In Cell ◽  
Spin Effects ◽  
Dimensional Phase Space ◽  
Spin Polarized ◽  
Underdense Plasma

We propose a numerical scheme to solve the semiclassical Vlasov–Maxwell equations for electrons with spin. The electron gas is described by a distribution function $f(t,{\boldsymbol x},{{{\boldsymbol p}}}, {\boldsymbol s})$ that evolves in an extended 9-dimensional phase space $({\boldsymbol x},{{{\boldsymbol p}}}, {\boldsymbol s})$ , where $\boldsymbol s$ represents the spin vector. Using suitable approximations and symmetries, the extended phase space can be reduced to five dimensions: $(x,{{p_x}}, {\boldsymbol s})$ . It can be shown that the spin Vlasov–Maxwell equations enjoy a Hamiltonian structure that motivates the use of the recently developed geometric particle-in-cell (PIC) methods. Here, the geometric PIC approach is generalized to the case of electrons with spin. Total energy conservation is very well satisfied, with a relative error below $0.05\,\%$ . As a relevant example, we study the stimulated Raman scattering of an electromagnetic wave interacting with an underdense plasma, where the electrons are partially or fully spin polarized. It is shown that the Raman instability is very effective in destroying the electron polarization.

scholarly journals Metastable Intermediates as Stepping Stones on the Maturation Pathways of Viral Capsids

mBio ◽  
2014 ◽  
Vol 5 (6) ◽  
Author(s):  
Giovanni Cardone ◽  
Robert L. Duda ◽  
Naiqian Cheng ◽  
Lili You ◽  
James F. Conway ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Large Scale ◽  
Structural Changes ◽  
Energy Landscape ◽  
Potential Hazard ◽  
Stepping Stones ◽  
Scanning Calorimetry ◽  
Conformational Effects ◽  
Capsid Maturation ◽  
Capsid Integrity

ABSTRACT As they mature, many capsids undergo massive conformational changes that transform their stability, reactivity, and capacity for DNA. In some cases, maturation proceeds via one or more intermediate states. These structures represent local minima in a rich energy landscape that combines contributions from subunit folding, association of subunits into capsomers, and intercapsomer interactions. We have used scanning calorimetry and cryo-electron microscopy to explore the range of capsid conformations accessible to bacteriophage HK97. To separate conformational effects from those associated with covalent cross-linking (a stabilization mechanism of HK97), a cross-link-incompetent mutant was used. The mature capsid Head I undergoes an endothermic phase transition at 60°C in which it shrinks by 7%, primarily through changes in its hexamer conformation. The transition is reversible, with a half-life of ~3 min; however, >50% of reverted capsids are severely distorted or ruptured. This observation implies that such damage is a potential hazard of large-scale structural changes such as those involved in maturation. Assuming that the risk is lower for smaller changes, this suggests a rationalization for the existence of metastable intermediates: that they serve as stepping stones that preserve capsid integrity as it switches between the radically different conformations of its precursor and mature states. IMPORTANCE Large-scale conformational changes are widespread in virus maturation and infection processes. These changes are accompanied by the release of conformational free energy as the virion (or fusogenic glycoprotein) switches from a precursor state to its mature state. Each state corresponds to a local minimum in an energy landscape. The conformational changes in capsid maturation are so radical that the question arises of how maturing capsids avoid being torn apart. Offering proof of principle, severe damage is inflicted when a bacteriophage HK97 capsid reverts from the (nonphysiological) state that it enters when heated past 60°C. We suggest that capsid proteins have been selected in part by the criterion of being able to avoid sustaining collateral damage as they mature. One way of achieving this—as with the HK97 capsid—involves breaking the overall transition down into several smaller steps in which the risk of damage is reduced.

scholarly journals Dynamical properties and extremes of Northern Hemisphere climate fields over the past 60 years

2017 ◽  
Vol 24 (4) ◽  
pp. 713-725 ◽  
Author(s):  
Davide Faranda ◽  
Gabriele Messori ◽  
M. Carmen Alvarez-Castro ◽  
Pascal Yiou
Keyword(s):  
Phase Space ◽  
Sea Level ◽  
Northern Hemisphere ◽  
Atmospheric Dynamics ◽  
Complex Nature ◽  
Human Welfare ◽  
Sea Level Pressure ◽  
Level Pressure ◽  
Dimensional Phase Space ◽  
Dynamical Properties

Abstract. Atmospheric dynamics are described by a set of partial differential equations yielding an infinite-dimensional phase space. However, the actual trajectories followed by the system appear to be constrained to a finite-dimensional phase space, i.e. a strange attractor. The dynamical properties of this attractor are difficult to determine due to the complex nature of atmospheric motions. A first step to simplify the problem is to focus on observables which affect – or are linked to phenomena which affect – human welfare and activities, such as sea-level pressure, 2 m temperature, and precipitation frequency. We make use of recent advances in dynamical systems theory to estimate two instantaneous dynamical properties of the above fields for the Northern Hemisphere: local dimension and persistence. We then use these metrics to characterize the seasonality of the different fields and their interplay. We further analyse the large-scale anomaly patterns corresponding to phase-space extremes – namely time steps at which the fields display extremes in their instantaneous dynamical properties. The analysis is based on the NCEP/NCAR reanalysis data, over the period 1948–2013. The results show that (i) despite the high dimensionality of atmospheric dynamics, the Northern Hemisphere sea-level pressure and temperature fields can on average be described by roughly 20 degrees of freedom; (ii) the precipitation field has a higher dimensionality; and (iii) the seasonal forcing modulates the variability of the dynamical indicators and affects the occurrence of phase-space extremes. We further identify a number of robust correlations between the dynamical properties of the different variables.

scholarly journals Free energy landscape for the entire transport cycle of triose-phosphate/phosphate translocator

2017 ◽  
Author(s):  
Mizuki Takemoto ◽  
Yongchan Lee ◽  
Ryuichiro Ishitani ◽  
Osamu Nureki
Keyword(s):  
Free Energy ◽  
Conformational Changes ◽  
Conformational Transition ◽  
Substrate Binding ◽  
Energy Landscape ◽  
Umbrella Sampling ◽  
Free Energy Landscape ◽  
Coupling Mechanism ◽  
Triose Phosphate ◽  
Phosphate Translocator

AbstractSecondary active transporters translocate their substrates using the electrochemical potentials of other chemicals, undergoing large-scale conformational changes. Despite extensive structural studies, the atomic details of the transport mechanism still remain elusive. Here we performed a series of all-atom molecular dynamics simulations of the triose-phosphate/phosphate translocator (TPT), which exports organic phosphates in the chloroplast stroma in strict counter exchange with inorganic phosphate (Pi). Biased sampling methods, including string method and umbrella sampling, successfully reproduced the conformational changes between the inward– and outward-facing states, along with the substrate binding. The free energy landscape of this entire TPT transition pathway demonstrated the alternating access and substrate translocation mechanisms, which revealed Pi is relayed by positively charged residues along the transition pathway. Furthermore, the conserved Glu207 functions as a “molecular switch”, linking the local substrate binding and the global conformational transition. Our results provide atomic-detailed insights into the energy coupling mechanism of antiporter.

scholarly journals Effects of Vegetation and Topography on the Boundary Layer Structure above the Amazon Forest

2020 ◽  
Vol 77 (8) ◽  
pp. 2941-2957
Author(s):  
Marcelo Chamecki ◽  
Livia S. Freire ◽  
Nelson L. Dias ◽  
Bicheng Chen ◽  
Cléo Quaresma Dias-Junior ◽  
...  
Keyword(s):  
Boundary Layer ◽  
Phase Space ◽  
Vertical Structure ◽  
Layer Structure ◽  
Roughness Sublayer ◽  
Large Contribution ◽  
Amazon Forest ◽  
Two Dimensional ◽  
Dimensional Phase Space ◽  
Field Campaigns

Abstract Observational data from two field campaigns in the Amazon forest were used to study the vertical structure of turbulence above the forest. The analysis was performed using the reduced turbulent kinetic energy (TKE) budget and its associated two-dimensional phase space. Results revealed the existence of two regions within the roughness sublayer in which the TKE budget cannot be explained by the canonical flat-terrain TKE budgets in the canopy roughness sublayer or in the lower portion of the convective ABL. Data analysis also suggested that deviations from horizontal homogeneity have a large contribution to the TKE budget. Results from LES of a model canopy over idealized topography presented similar features, leading to the conclusion that flow distortions caused by topography are responsible for the observed features in the TKE budget. These results support the conclusion that the boundary layer above the Amazon forest is strongly impacted by the gentle topography underneath.

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