scholarly journals A Favorable Path to Domain Separation in the Orange Carotenoid Protein

2021 ◽  
Author(s):  
Mahmoud Sharawy ◽  
Natalia B. Pigni ◽  
Eric R. May ◽  
José A. Gascón
Keyword(s):  
Free Energy ◽  
Conformational Changes ◽  
Defense Mechanism ◽  
Optimization Methods ◽  
Free Energy Surface ◽  
Pathway Optimization ◽  
Orange Carotenoid Protein ◽  
Probable Path ◽  
Most Probable Path ◽  
Domain Separation

The Orange Carotenoid Protein (OCP) is responsible for nonphotochemical quenching (NPQ) in cyanobacteria, a defense mechanism against potentially damaging effects of excess light conditions. This soluble two-domain protein undergoes profound conformational changes upon photoactivation, involving translocation of the ketocarotenoid inside the cavity followed by domain separation. Domain separation is a critical step in the photocycle of OCP because it exposes the N-terminal domain (NTD) to perform quenching of the phycobilisomes. Many details regarding the mechanism and energetics of OCP domain separation remain unknown. In this work, we apply metadynamics to elucidate the protein rearrangements that lead to the active, domain-separated, form of OCP. We find that translocation of the ketocarotenoid canthaxanthin has a profound effect on the energetic landscape and that domain separation only becomes favorable following translocation. We further explore, characterize, and validate the free energy surface (FES) using equilibrium simulations initiated from different states on the FES. Through pathway optimization methods, we characterize the most probable path to domain separation and reveal the barriers along that pathway. We find that the free energy barriers are relatively small (<5 kcal/mol), but the overall estimated kinetic rate is consistent with experimental measurements (>1 ms). Overall, our results provide detailed information on the requirement for canthaxanthin translocation to precede domain separation and an energetically feasible pathway to dissociation.

scholarly journals A Favorable Path to Domain Separation in the Orange Carotenoid Protein

2021 ◽  
Author(s):  
Mahmoud Sharawy ◽  
Natalia B. Pigni ◽  
Eric R. May ◽  
José A. Gascón
Keyword(s):  
Defense Mechanism ◽  
Protein Domains ◽  
Structural Rearrangement ◽  
Light Conditions ◽  
Structural Rearrangements ◽  
Fundamental Part ◽  
Activated State ◽  
Orange Carotenoid Protein ◽  
Standing Question ◽  
Domain Separation

In this work, we have modeled a fundamental part of the defense mechanism of Cyanobacteria against damaging effects of excess light conditions. This mechanism is part of the photoactivation cycle in the Orange Carotenoid Protein (OCP), which involves the separation of protein domains triggered by chromophore translocation. Using carefully designed metadynamics simulations, we have discovered the structural rearrangements along an energetically favorable pathway to the activated state. The structural rearrangement of OCP along its activation path has been a long-standing question, only answered now by our work.<br>

Computational insight into the anticholinesterase activities and electronic properties of physostigmine analogs

2019 ◽  
Vol 11 (15) ◽  
pp. 1907-1928 ◽  
Author(s):  
Adebayo A Adeniyi ◽  
Jeanet Conradie
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Quantum Mechanics ◽  
Structural Properties ◽  
Conformational Changes ◽  
Energy Surface ◽  
Binding Free Energy ◽  
The Elderly ◽  
Free Energy Surface ◽  
Insight Into

Aim: Alzheimer's disease (AD) is known to be themajor cause of dementia among the elderly. The structural properties and binding interactions of the AD drug physostigmine (-)-phy, and its analogues (-)-hex and (-)-phe and (+)-phe, were examined, as well as their impact on the conformational changes of two different AD target enzymes AChE and BChE. Materials & methods: The conformational changes were studied using molecular dynamics and structural properties using Quantum mechanics. Results & conclusions: The binding free energy (ΔGbind) and the change in the free energy surface (FES) computed from the funnel metadynamics (FMD) simulation, both support the idea that inhibitors (-)-phe and (-)-hex have better binding activities toward enzyme AChE, and that (-)-phe is stronger in binding than the present AD drug (-)-phy.

scholarly journals A Favorable Path to Domain Separation in the Orange Carotenoid Protein

2021 ◽  
Author(s):  
Mahmoud Sharawy ◽  
Natalia B. Pigni ◽  
Eric R. May ◽  
José A. Gascón
Keyword(s):  
Defense Mechanism ◽  
Protein Domains ◽  
Structural Rearrangement ◽  
Light Conditions ◽  
Structural Rearrangements ◽  
Fundamental Part ◽  
Activated State ◽  
Orange Carotenoid Protein ◽  
Standing Question ◽  
Domain Separation

In this work, we have modeled a fundamental part of the defense mechanism of Cyanobacteria against damaging effects of excess light conditions. This mechanism is part of the photoactivation cycle in the Orange Carotenoid Protein (OCP), which involves the separation of protein domains triggered by chromophore translocation. Using carefully designed metadynamics simulations, we have discovered the structural rearrangements along an energetically favorable pathway to the activated state. The structural rearrangement of OCP along its activation path has been a long-standing question, only answered now by our work.<br>

Molecular Basis of Glucose Transport Mechanism in Plants

2019 ◽  
Author(s):  
Balaji Selvam ◽  
Ya-Chi Yu ◽  
Liqing Chen ◽  
Diwakar Shukla
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Transport Mechanism ◽  
Conformational Dynamics ◽  
Site Directed Mutagenesis ◽  
Free Energy Barrier ◽  
Transport Cycle ◽  
Dynamics Simulations

<p>The SWEET family belongs to a class of transporters in plants that undergoes large conformational changes to facilitate transport of sugar molecules across the cell membrane. However, the structures of their functionally relevant conformational states in the transport cycle have not been reported. In this study, we have characterized the conformational dynamics and complete transport cycle of glucose in OsSWEET2b transporter using extensive molecular dynamics simulations. Using Markov state models, we estimated the free energy barrier associated with different states as well as 1 for the glucose the transport mechanism. SWEETs undergoes structural transition to outward-facing (OF), Occluded (OC) and inward-facing (IF) and strongly support alternate access transport mechanism. The glucose diffuses freely from outside to inside the cell without causing major conformational changes which means that the conformations of glucose unbound and bound snapshots are exactly same for OF, OC and IF states. We identified a network of hydrophobic core residues at the center of the transporter that restricts the glucose entry to the cytoplasmic side and act as an intracellular hydrophobic gate. The mechanistic predictions from molecular dynamics simulations are validated using site-directed mutagenesis experiments. Our simulation also revealed hourglass like intermediate states making the pore radius narrower at the center. This work provides new fundamental insights into how substrate-transporter interactions actively change the free energy landscape of the transport cycle to facilitate enhanced transport activity.</p>

scholarly journals Exploration of Free Energy Surface and Thermal Effects on Relative Population and Infrared Spectrum of the Be6B11− Fluxional Cluster

Materials ◽  
2020 ◽  
Vol 14 (1) ◽  
pp. 112
Author(s):  
Carlos Emiliano Buelna-Garcia ◽  
José Luis Cabellos ◽  
Jesus Manuel Quiroz-Castillo ◽  
Gerardo Martinez-Guajardo ◽  
Cesar Castillo-Quevedo ◽  
...  
Keyword(s):  
Free Energy ◽  
Infrared Spectrum ◽  
Infrared Spectra ◽  
Thermal Effects ◽  
Global Minimum ◽  
Energy Surface ◽  
Weighted Sums ◽  
Free Energy Surface ◽  
Temperature Dependent ◽  
Relative Population

The starting point to understanding cluster properties is the putative global minimum and all the nearby local energy minima; however, locating them is computationally expensive and difficult. The relative populations and spectroscopic properties that are a function of temperature can be approximately computed by employing statistical thermodynamics. Here, we investigate entropy-driven isomers distribution on Be6B11− clusters and the effect of temperature on their infrared spectroscopy and relative populations. We identify the vibration modes possessed by the cluster that significantly contribute to the zero-point energy. A couple of steps are considered for computing the temperature-dependent relative population: First, using a genetic algorithm coupled to density functional theory, we performed an extensive and systematic exploration of the potential/free energy surface of Be6B11− clusters to locate the putative global minimum and elucidate the low-energy structures. Second, the relative populations’ temperature effects are determined by considering the thermodynamic properties and Boltzmann factors. The temperature-dependent relative populations show that the entropies and temperature are essential for determining the global minimum. We compute the temperature-dependent total infrared spectra employing the Boltzmann factor weighted sums of each isomer’s infrared spectrum and find that at finite temperature, the total infrared spectrum is composed of an admixture of infrared spectra that corresponds to the spectra of the lowest-energy structure and its isomers located at higher energies. The methodology and results describe the thermal effects in the relative population and the infrared spectra.

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