scholarly journals Variation of free-energy landscape of the p53 C-terminal domain induced by acetylation: Enhanced conformational sampling

2016 ◽  
Vol 37 (31) ◽  
pp. 2687-2700 ◽  
Author(s):  
Shinji Iida ◽  
Tadaaki Mashimo ◽  
Takashi Kurosawa ◽  
Hironobu Hojo ◽  
Hiroya Muta ◽  
...  
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Conformational Sampling ◽  
Terminal Domain

scholarly journals Enhanced conformational sampling to visualize a free-energy landscape of protein complex formation

2016 ◽  
Vol 473 (12) ◽  
pp. 1651-1662 ◽  
Author(s):  
Shinji Iida ◽  
Haruki Nakamura ◽  
Junichi Higo
Keyword(s):  
Free Energy ◽  
Room Temperature ◽  
Dimensional Space ◽  
Energy Landscape ◽  
Complex Structure ◽  
Complex Form ◽  
Ensemble Methods ◽  
Ensemble Method ◽  
Free Energy Landscape ◽  
Conformational Sampling

We introduce various, recently developed, generalized ensemble methods, which are useful to sample various molecular configurations emerging in the process of protein–protein or protein–ligand binding. The methods introduced here are those that have been or will be applied to biomolecular binding, where the biomolecules are treated as flexible molecules expressed by an all-atom model in an explicit solvent. Sampling produces an ensemble of conformations (snapshots) that are thermodynamically probable at room temperature. Then, projection of those conformations to an abstract low-dimensional space generates a free-energy landscape. As an example, we show a landscape of homo-dimer formation of an endothelin-1-like molecule computed using a generalized ensemble method. The lowest free-energy cluster at room temperature coincided precisely with the experimentally determined complex structure. Two minor clusters were also found in the landscape, which were largely different from the native complex form. Although those clusters were isolated at room temperature, with rising temperature a pathway emerged linking the lowest and second-lowest free-energy clusters, and a further temperature increment connected all the clusters. This exemplifies that the generalized ensemble method is a powerful tool for computing the free-energy landscape, by which one can discuss the thermodynamic stability of clusters and the temperature dependence of the cluster networks.

scholarly journals Computational methods for exploring protein conformations

2020 ◽  
Vol 48 (4) ◽  
pp. 1707-1724
Author(s):  
Jane R. Allison
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Free Energy Landscape ◽  
Conformational Sampling ◽  
Conformational Ensemble ◽  
Collective Variables ◽  
Conformational States ◽  
Simulation Techniques ◽  
Wide Range ◽  
Dynamics Simulations

Proteins are dynamic molecules that can transition between a potentially wide range of structures comprising their conformational ensemble. The nature of these conformations and their relative probabilities are described by a high-dimensional free energy landscape. While computer simulation techniques such as molecular dynamics simulations allow characterisation of the metastable conformational states and the transitions between them, and thus free energy landscapes, to be characterised, the barriers between states can be high, precluding efficient sampling without substantial computational resources. Over the past decades, a dizzying array of methods have emerged for enhancing conformational sampling, and for projecting the free energy landscape onto a reduced set of dimensions that allow conformational states to be distinguished, known as collective variables (CVs), along which sampling may be directed. Here, a brief description of what biomolecular simulation entails is followed by a more detailed exposition of the nature of CVs and methods for determining these, and, lastly, an overview of the myriad different approaches for enhancing conformational sampling, most of which rely upon CVs, including new advances in both CV determination and conformational sampling due to machine learning.

Determination of Base Flipping Free Energy Landscapes from Nonequilibrium Stratification

2019 ◽  
Author(s):  
Xiaohui Wang ◽  
Zhaoxi Sun
Keyword(s):  
Free Energy ◽  
Energy Landscape ◽  
Sampling Technique ◽  
Umbrella Sampling ◽  
Energy Simulation ◽  
Nonlinear Dependence ◽  
Free Energy Landscape ◽  
Convergence Criterion ◽  
Base Flipping ◽  
Convergence Behavior

<p>Correct calculation of the variation of free energy upon base flipping is crucial in understanding the dynamics of DNA systems. The free energy landscape along the flipping pathway gives the thermodynamic stability and the flexibility of base-paired states. Although numerous free energy simulations are performed in the base flipping cases, no theoretically rigorous nonequilibrium techniques are devised and employed to investigate the thermodynamics of base flipping. In the current work, we report a general nonequilibrium stratification scheme for efficient calculation of the free energy landscape of base flipping in DNA duplex. We carefully monitor the convergence behavior of the equilibrium sampling based free energy simulation and the nonequilibrium stratification and determine the empirical length of time blocks required for converged sampling. Comparison between the performances of equilibrium umbrella sampling and nonequilibrium stratification is given. The results show that nonequilibrium free energy simulation is able to give similar accuracy and efficiency compared with the equilibrium enhanced sampling technique in the base flipping cases. We further test a convergence criterion we previously proposed and it comes out that the convergence behavior determined by this criterion agrees with those given by the time-invariant behavior of PMF and the nonlinear dependence of standard deviation on the sample size. </p>

The Perturbed Free Energy Landscape: Linking Ligand Binding to Biomolecular Folding

ChemBioChem ◽  
2020 ◽  
Author(s):  
fareed aboul-ela ◽  
Abdallah S Abdelsatter ◽  
Youssef Mansour
Keyword(s):  
Free Energy ◽  
Ligand Binding ◽  
Energy Landscape ◽  
Free Energy Landscape

Topography of the Free Energy Landscape on the Claisen-Schmidt Condensation: Solvent and Temperature Effect in the Rate-Controlling Step

2021 ◽  
Author(s):  
Nayara Dantas Coutinho ◽  
Hugo Gontijo Machado ◽  
Valter Henrique Carvalho-Silva ◽  
Wender A. Silva
Keyword(s):  
Free Energy ◽  
Temperature Effect ◽  
Strong Influence ◽  
Aldol Condensation ◽  
Energy Landscape ◽  
Bond Formation ◽  
Free Energy Landscape ◽  
Rate Controlling Step ◽  
Formation Step

Recent studies have assigned hydroxide elimination and C=C bond formation step in base-promoted aldol condensation the role of having a strong influence in the overall rate reaction, in contrast to...

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