scholarly journals Free-energy coarse-grained potential for C60

2015 ◽  
Vol 143 (16) ◽  
pp. 164509 ◽  
Author(s):  
D. M. Edmunds ◽  
P. Tangney ◽  
D. D. Vvedensky ◽  
W. M. C. Foulkes
Keyword(s):  
Free Energy ◽  
Coarse Grained

scholarly journals How proteins open fusion pores: insights from molecular simulations

2020 ◽  
Author(s):  
H. Jelger Risselada ◽  
Helmut Grubmüller
Keyword(s):  
Free Energy ◽  
Fusion Proteins ◽  
Graphics Processing Units ◽  
Fusion Reaction ◽  
Molecular Simulations ◽  
Minimum Free Energy ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Fusion Pore ◽  
Graphics Processing

AbstractFusion proteins can play a versatile and involved role during all stages of the fusion reaction. Their roles go far beyond forcing the opposing membranes into close proximity to drive stalk formation and fusion. Molecular simulations have played a central role in providing a molecular understanding of how fusion proteins actively overcome the free energy barriers of the fusion reaction up to the expansion of the fusion pore. Unexpectedly, molecular simulations have revealed a preference of the biological fusion reaction to proceed through asymmetric pathways resulting in the formation of, e.g., a stalk-hole complex, rim-pore, or vertex pore. Force-field based molecular simulations are now able to directly resolve the minimum free-energy path in protein-mediated fusion as well as quantifying the free energies of formed reaction intermediates. Ongoing developments in Graphics Processing Units (GPUs), free energy calculations, and coarse-grained force-fields will soon gain additional insights into the diverse roles of fusion proteins.

scholarly journals Distributions of experimental protein structures on coarse-grained free energy landscapes

2015 ◽  
Vol 143 (24) ◽  
pp. 243153 ◽  
Author(s):  
Kannan Sankar ◽  
Jie Liu ◽  
Yuan Wang ◽  
Robert L. Jernigan
Keyword(s):  
Free Energy ◽  
Protein Structures ◽  
Coarse Grained ◽  
Energy Landscapes ◽  
Free Energy Landscapes

COMPARING FOLDING MECHANISMS OF DIFFERENT PRION PROTEINS BY Gō MODEL

2013 ◽  
Vol 12 (08) ◽  
pp. 1341004
Author(s):  
XUE WU ◽  
TING FU ◽  
ZHI-LONG XIU ◽  
LIU YIN ◽  
JIN-GUANG WANG ◽  
...  
Keyword(s):  
Free Energy ◽  
Prion Protein ◽  
Energy Barrier ◽  
Prion Proteins ◽  
Coarse Grained ◽  
Transmissible Spongiform Encephalopathies ◽  
Free Energy Barrier ◽  
Spongiform Encephalopathies ◽  
Go Model ◽  
Folding Free Energy

Prions are associated with neurodegenerative diseases induced by transmissible spongiform encephalopathies. The infectious scrapie form is referred to as PrP Sc , which has conformational change from normal prion with predominant α-helical conformation to the abnormal PrP Sc that is rich in β-sheet content. Neurodegenerative diseases have been found from both human and bovine sources, but there are no reports about infected by transmissible spongiform encephalopathies from rabbit, canine and horse sources. Here we used coarse-grained Gō model to compare the difference among human, bovine, rabbit, canine, and horse normal (cellular) prion proteins. The denatured state of normal prion has relation with the conversion from normal to abnormal prion protein, so we used all-atom Gō model to investigate the folding pathway and energy landscape for human prion protein. Through using coarse-grained Gō model, the cooperativity of the five prion proteins was characterized in terms of calorimetric criterion, sigmoidal transition, and free-energy profile. The rabbit and horse prion proteins have higher folding free-energy barrier and cooperativity, and canine prion protein has slightly higher folding free-energy barrier comparing with human and bovine prion proteins. The results from all-atom Gō model confirmed the validity of C α-Gō model. The correlations of our results with previous experimental and theoretical researches were discussed.

scholarly journals Simulation of FUS protein condensates with an adapted coarse-grained model

2020 ◽  
Author(s):  
Zakarya Benayad ◽  
Sören von Bülow ◽  
Lukas S. Stelzl ◽  
Gerhard Hummer
Keyword(s):  
Free Energy ◽  
Phase Separation ◽  
Potential Energy ◽  
Energy Function ◽  
Potential Energy Function ◽  
Scaling Factor ◽  
Coarse Grained ◽  
Disordered Proteins ◽  
General Strategy ◽  
Droplet Shape

AbstractDisordered proteins and nucleic acids can condense into droplets that resemble the membraneless organelles observed in living cells. MD simulations offer a unique tool to characterize the molecular interactions governing the formation of these biomolecular condensates, their physico-chemical properties, and the factors controlling their composition and size. However, biopolymer condensation depends sensitively on the balance between different energetic and entropic contributions. Here, we develop a general strategy to fine-tune the potential energy function for molecular dynamics simulations of biopolymer phase separation. We rebalance protein-protein interactions against solvation and entropic contributions to match the excess free energy of transferring proteins between dilute solution and condensate. We illustrate this formalism by simulating liquid droplet formation of the FUS low complexity domain (LCD) with a rebalanced MARTINI model. By scaling the strength of the nonbonded interactions in the coarse-grained MARTINI potential energy function, we map out a phase diagram in the plane of protein concentration and interaction strength. Above a critical scaling factor of αc ≈ 0.6, FUS LCD condensation is observed, where α = 1 and 0 correspond to full and repulsive interactions in the MARTINI model, respectively. For a scaling factor α = 0.65, we recover the experimental densities of the dilute and dense phases, and thus the excess protein transfer free energy into the droplet and the saturation concentration where FUS LCD condenses. In the region of phase separation, we simulate FUS LCD droplets of four different sizes in stable equilibrium with the dilute phase and slabs of condensed FUS LCD for tens of microseconds, and over one millisecond in aggregate. We determine surface tensions in the range of 0.01 to 0.4mN/m from the fluctuations of the droplet shape and from the capillary-wave-like broadening of the interface between the two phases. From the dynamics of the protein end-to-end distance, we estimate shear viscosities from 0.001 to 0.02Pas for the FUS LCD droplets with scaling factors α in the range of 0.625 to 0.75, where we observe liquid droplets. Significant hydration of the interior of the droplets keeps the proteins mobile and the droplets fluid.

scholarly journals ‘Martinizing’ the Variational Implicit Solvent Method (VISM): Solvation Free Energy for Coarse-Grained Proteins

2018 ◽  
Vol 114 (3) ◽  
pp. 344a-345a
Author(s):  
Clarisse Gravina Ricci ◽  
Bo Li ◽  
Li-Tien Cheng ◽  
Joachim Dzubiella ◽  
J. Andrew McCammon
Keyword(s):  
Free Energy ◽  
Solvation Free Energy ◽  
Coarse Grained ◽  
Implicit Solvent ◽  
Solvent Method

scholarly journals Dissecting the role of the γ-subunit in the rotary–chemical coupling and torque generation of F1-ATPase

2015 ◽  
Vol 112 (9) ◽  
pp. 2746-2751 ◽  
Author(s):  
Shayantani Mukherjee ◽  
Arieh Warshel
Keyword(s):  
Free Energy ◽  
Atp Hydrolysis ◽  
Mechanical Energy ◽  
Coarse Grained ◽  
Γ Subunit ◽  
Torque Generation ◽  
Chemical Coupling ◽  
Basic Features ◽  
Experimental Findings ◽  
Molecular Nature

Unraveling the molecular nature of the conversion of chemical energy (ATP hydrolysis in the α/β-subunits) to mechanical energy and torque (rotation of the γ-subunit) in F1-ATPase is very challenging. A major part of the challenge involves understanding the rotary–chemical coupling by a nonphenomenological structure–energy description, while accounting for the observed torque generated on the γ-subunit and its change due to mutation of this unit. Here we extend our previous study that used a coarse-grained model of the F1-ATPase to generate a structure-based free energy landscape of the rotary–chemical process. Our quantitative analysis of the landscape reproduced the observed torque for the wild-type enzyme. In doing so, we found that there are several possibilities of torque generation from landscapes with various shapes and demonstrated that a downhill slope along the chemical coordinate could still result in negligible torque, due to ineffective coupling of the chemistry to the γ-subunit rotation. We then explored the relationship between the functionality and the underlying sequence through systematic examination of the effect of various parts of the γ-subunit on free energy surfaces of F1-ATPase. Furthermore, by constructing several types of γ-deletion systems and calculating the corresponding torque generation, we gained previously unknown insights into the molecular nature of the F1-ATPase rotary motor. Significantly, our results are in excellent agreement with recent experimental findings and indicate that the rotary–chemical coupling is primarily established through electrostatic effects, although specific contacts through γ-ionizable residue side chains are not essential for establishing the basic features of the coupling.

scholarly journals Molecular stripping in theNF-κB/IκB/DNAgenetic regulatory network

2015 ◽  
Vol 113 (1) ◽  
pp. 110-115 ◽  
Author(s):  
Davit A. Potoyan ◽  
Weihua Zheng ◽  
Elizabeth A. Komives ◽  
Peter G. Wolynes
Keyword(s):  
Free Energy ◽  
Transcription Factor ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Genetic Switch ◽  
Binary And Ternary Complexes ◽  
Landscape Models ◽  
Gene Switches ◽  
Dna Release ◽  
Dynamics Simulations

Genetic switches based on theNF-κB/IκB/DNAsystem are master regulators of an array of cellular responses. Recent kinetic experiments have shown thatIκBcan actively removeNF-κBbound to its genetic sites via a process called “molecular stripping.” This allows theNF-κB/IκB/DNAswitch to function under kinetic control rather than the thermodynamic control contemplated in the traditional models of gene switches. Using molecular dynamics simulations of coarse-grained predictive energy landscape models for the constituent proteins by themselves and interacting with the DNA we explore the functional motions of the transcription factorNF-κBand its various binary and ternary complexes with DNA and the inhibitorIκB. These studies show that the function of theNF-κB/IκB/DNAgenetic switch is realized via an allosteric mechanism. Molecular stripping occurs through the activation of a domain twist mode by the binding ofIκBthat occurs through conformational selection. Free energy calculations for DNA binding show that the binding ofIκBnot only results in a significant decrease of the affinity of the transcription factor for the DNA but also kinetically speeds DNA release. Projections of the free energy onto various reaction coordinates reveal the structural details of the stripping pathways.

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