Erratum to ‘Multi-Scale Free Energy Landscape calculation method by combination of coarse-grained and all-atom models’ [Chem. Phys. Lett. 503 (2011) 145–152]

2011 ◽  
Vol 516 (1-3) ◽  
pp. 113 ◽  
Author(s):  
Ryuhei Harada ◽  
Akio Kitao
Keyword(s):  
Free Energy ◽  
Calculation Method ◽  
Energy Landscape ◽  
Chem Phys ◽  
Coarse Grained ◽  
Free Energy Landscape ◽  
Scale Free ◽  
Multi Scale

scholarly journals Comment on “Communication: Benzene dimer—The free energy landscape” [J. Chem. Phys. 139, 201102 (2013)]

2014 ◽  
Vol 140 (22) ◽  
pp. 227101 ◽  
Author(s):  
Ad van der Avoird ◽  
Rafał Podeszwa ◽  
Bernd Ensing ◽  
Krzysztof Szalewicz
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Chem Phys ◽  
Free Energy Landscape ◽  
Benzene Dimer

scholarly journals Accurate protein-folding transition-path statistics from a simple free-energy landscape

2018 ◽  
Author(s):  
William M. Jacobs ◽  
Eugene I. Shakhnovich
Keyword(s):  
Free Energy ◽  
Protein Folding ◽  
Energy Landscape ◽  
Coarse Grained ◽  
Free Energy Landscape ◽  
Configuration Model ◽  
Trajectory Data ◽  
Transition Path ◽  
One Dimensional ◽  
Transition Paths

A central goal of protein-folding theory is to predict the stochastic dynamics of transition paths — the rare trajectories that transit between the folded and unfolded ensembles — using only thermodynamic information, such as a low-dimensional equilibrium free-energy landscape. However, commonly used one-dimensional landscapes typically fall short of this aim, because an empirical coordinate-dependent diffusion coefficient has to be fit to transition-path trajectory data in order to reproduce the transition-path dynamics. We show that an alternative, first-principles free-energy landscape predicts transition-path statistics that agree well with simulations and single-molecule experiments without requiring dynamical data as an input. This ‘topological configuration’ model assumes that distinct, native-like substructures assemble on a timescale that is slower than native-contact formation but faster than the folding of the entire protein. Using only equilibrium simulation data to determine the free energies of these coarse-grained intermediate states, we predict a broad distribution of transition-path transit times that agrees well with the transition-path durations observed in simulations. We further show that both the distribution of finite-time displacements on a one-dimensional order parameter and the ensemble of transition-path trajectories generated by the model are consistent with the simulated transition paths. These results indicate that a landscape based on transient folding intermediates, which are often hidden by one-dimensional projections, can form the basis of a predictive model of protein-folding transition-path dynamics.

scholarly journals Exploring the free-energy landscape of GPCR activation

2018 ◽  
Vol 115 (41) ◽  
pp. 10327-10332 ◽  
Author(s):  
Raphael Alhadeff ◽  
Igor Vorobyov ◽  
Han Wool Yoon ◽  
Arieh Warshel
Keyword(s):  
Free Energy ◽  
Structural Information ◽  
Large Fraction ◽  
Energy Landscape ◽  
Point Of View ◽  
Coarse Grained ◽  
Free Energy Landscape ◽  
Activation Process ◽  
Gpcr Activation ◽  
Membrane Bound

G-protein–coupled receptors (GPCRs) are a large group of membrane-bound receptor proteins that are involved in a plethora of diverse processes (e.g., vision, hormone response). In mammals, and particularly in humans, GPCRs are involved in many signal transduction pathways and, as such, are heavily studied for their immense pharmaceutical potential. Indeed, a large fraction of drugs target various GPCRs, and drug-development is often aimed at GPCRs. Therefore, understanding the activation of GPCRs is a challenge of major importance both from fundamental and practical considerations. And yet, despite the remarkable progress in structural understanding, we still do not have a translation of the structural information to an energy-based picture. Here we use coarse-grained (CG) modeling to chart the free-energy landscape of the activation process of the β-2 adrenergic receptor (β2AR) as a representative GPCR. The landscape provides the needed tool for analyzing the processes that lead to activation of the receptor upon binding of the ligand (adrenaline) while limiting constitutive activation. Our results pave the way to better understand the biological mechanisms of action of the β2AR and GPCRs, from a physical chemistry point of view rather than simply by observing the receptor’s behavior physiologically.

scholarly journals Torque, chemistry and efficiency in molecular motors: a study of the rotary–chemical coupling in F1-ATPase

2015 ◽  
Vol 48 (4) ◽  
pp. 395-403 ◽  
Author(s):  
Shayantani Mukherjee ◽  
Ram Prasad Bora ◽  
Arieh Warshel
Keyword(s):  
Free Energy ◽  
Molecular Motors ◽  
Energy Landscape ◽  
Molecular Machine ◽  
Coarse Grained ◽  
Free Energy Landscape ◽  
Thermodynamic Efficiency ◽  
Rotational Angle ◽  
Torque Generation ◽  
Chemical Coupling

AbstractDetailed understanding of the action of biological molecular machines must overcome the challenge of gaining a clear knowledge of the corresponding free-energy landscape. An example for this is the elucidation of the nature of converting chemical energy to torque and work in the rotary molecular motor of F1-ATPase. A major part of the challenge involves understanding the rotary–chemical coupling from a non-phenomenological structure/energy description. Here we focused on using a coarse-grained model of F1-ATPase to generate a structure-based free-energy landscape of the rotary–chemical process of the whole system. In particular, we concentrated on exploring the possible impact of the position of the catalytic dwell on the efficiency and torque generation of the molecular machine. It was found that the experimentally observed torque can be reproduced with landscapes that have different positions for the catalytic dwell on the rotary–chemical surface. Thus, although the catalysis is undeniably required for torque generation, the experimentally observed position of the catalytic dwell at 80° might not have a clear advantage for the force generation by F1-ATPase. This further implies that the rotary–chemical couplings in these biological motors are quite robust and their efficiencies do not depend explicitly on the position of the catalytic dwells. Rather, the specific positioning of the dwells with respect to the rotational angle is a characteristic arising due to the structural construct of the molecular machine and might not bear any clear connection to the thermodynamic efficiency for the system.

scholarly journals A Free-Energy Landscape Analysis of Calmodulin Obtained from an NMR Data-Utilized Multi-Scale Divide-and-Conquer Molecular Dynamics Simulation

Life ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1241
Author(s):  
Hiromitsu Shimoyama ◽  
Yasuteru Shigeta
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Structural Change ◽  
Conformational Changes ◽  
Calcium Binding ◽  
Structural Changes ◽  
Energy Landscape ◽  
Divide And Conquer ◽  
Free Energy Landscape ◽  
Multi Scale

Calmodulin (CaM) is a multifunctional calcium-binding protein, which regulates a variety of biochemical processes. CaM acts through its conformational changes and complex formation with its target enzymes. CaM consists of two globular domains (N-lobe and C-lobe) linked by an extended linker region. Upon calcium binding, the N-lobe and C-lobe undergo local conformational changes, followed by a major conformational change of the entire CaM to wrap the target enzyme. However, the regulation mechanisms, such as allosteric interactions, which regulate the large structural changes, are still unclear. In order to investigate the series of structural changes, the free-energy landscape of CaM was obtained by multi-scale divide-and-conquer molecular dynamics (MSDC-MD). The resultant free-energy landscape (FEL) shows that the Ca2+ bound CaM (holo-CaM) would take an experimentally famous elongated structure, which can be formed in the early stage of structural change, by breaking the inter-domain interactions. The FEL also shows that important interactions complete the structural change from the elongated structure to the ring-like structure. In addition, the FEL might give a guiding principle to predict mutational sites in CaM. In this study, it was demonstrated that the movement process of macroscopic variables on the FEL may be diffusive to some extent, and then, the MSDC-MD is suitable to the parallel computation.

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