scholarly journals Residue-Residue Mutual Work Analysis of Retinal-Opsin Interaction in Rhodopsin: Implications for Protein-Ligand Binding

2019 ◽  
Author(s):  
Wenjin Li
Keyword(s):  
Virtual Work ◽  
Interaction Matrix ◽  
Time Interval ◽  
Transition Path ◽  
Transition Path Sampling ◽  
Decomposition Approach ◽  
Work Analysis ◽  
Nmr Study ◽  
The Matrix ◽  
Dynamics Simulations

AbstractEnergetic contributions at single-residue level to retinal-opsin interaction in rhodopsin were studied by combining molecular dynamics simulations, transition path sampling, and a newly developed energy decomposition approach. The virtual work at an infinitesimal time interval was decomposed into the work components on one residue due to its interaction with another residue, which were then averaged over the transition path ensemble along a proposed reaction coordinate. Such residue-residue mutual work analysis on 62 residues within the active center of rhodopsin resulted in a very sparse interaction matrix, which is generally not symmetric but anti-symmetric to some extent. 14 residues were identified to be major players in retinal relaxation, which is in excellent agreement with an existing NMR study. Based on the matrix of mutual work, a comprehensive network was constructed to provide detailed insights into the chromophore-protein interaction from a viewpoint of energy flow.

scholarly journals Microscopic interpretation of folding ϕ-values using the transition path ensemble

2016 ◽  
Vol 113 (12) ◽  
pp. 3263-3268 ◽  
Author(s):  
Robert B. Best ◽  
Gerhard Hummer
Keyword(s):  
Transition Path ◽  
Transition Path Sampling ◽  
Mutant Proteins ◽  
Transition Path Theory ◽  
Folding Rates ◽  
Small Proteins ◽  
Versus Transition ◽  
Microscopic Interpretation ◽  
Dynamics Simulations ◽  
Substantial Heterogeneity

All-atom molecular dynamics simulations now allow us to create movies of proteins folding and unfolding. However, it is difficult to assess the accuracy of the folding mechanisms observed because experiments cannot yet directly resolve events occurring along the transition paths between unfolded and folded states. Protein folding ϕ-values provide residue-resolved information about folding mechanisms by comparing the effects of mutations on folding rates and stability, but determining ϕ-values by separately simulating mutant proteins would be computationally demanding and prone to large statistical errors. Here we use transition path theory to develop a method for computing ϕ-values directly from the transition path ensemble, without the need for additional simulations. This path-based approach uses the full transition path information available from equilibrium folding and unfolding trajectories, or from transition path sampling, and does not require identification of folding transition states. Applying our approach to a set of simulations of 10 small proteins by Shaw and coworkers [Lindorff-Larsen K, Piana S, Dror RO, Shaw DE (2011) Science 334(6055):517–520; Piana S, Lindorff-Larsen K, Shaw DE (2011) Biophys J 100(9):L47–L49; and Piana S, Lindorff-Larsen K, Shaw DE (2013) Proc Natl Acad Sci USA 110(15):5915–5920], we find good agreement with experiments in most cases where data are available. We can further resolve the contributions to fractional ϕ-values coming from partial contact formation versus transition path heterogeneity. Although in some cases, there is substantial heterogeneity of folding mechanism, in others, such as Ubiquitin, the mechanism is strongly conserved.

scholarly journals OpenPathSampling: A Python framework for path sampling simulations. I. Basics

2018 ◽  
Author(s):  
David W.H. Swenson ◽  
Jan-Hendrik Prinz ◽  
Frank Noe ◽  
John D. Chodera ◽  
Peter G. Bolhuis
Keyword(s):  
Benchmark Problems ◽  
Path Sampling ◽  
Transition Path ◽  
Transition Path Sampling ◽  
Molecular Systems ◽  
Sampling Schemes ◽  
Initial Release ◽  
Sampling Algorithms ◽  
Dynamics Simulations ◽  
Transition Interface

Transition path sampling techniques allow molecular dynamics simulations of complex systems to focuson rare dynamical events, providing insight into mechanisms and the ability to calculate rates inaccessibleby ordinary dynamics simulations. While path sampling algorithms are conceptually as simple as importancesampling Monte Carlo, the technical complexity of their implementation has kept these techniquesout of reach of the broad community. Here, we introduce an easy-to-use Python framework called Open-PathSampling (OPS) that facilitates path sampling for (bio)molecular systems with minimal effort and yetis still extensible. Interfaces to OpenMM and an internal dynamics engine for simple models are providedin the initial release, but new molecular simulation packages can easily be added. Multiple ready-to-usetransition path sampling methodologies are implemented, including standard transition path sampling (TPS)between reactant and product states, transition interface sampling (TIS) and its replica exchange variant(RETIS), as well as recent multistate and multiset extensions of transition interface sampling (MSTIS, MISTIS).In addition, tools are provided to facilitate the implementation of new path sampling schemes built on basicpath sampling components. In this paper, we give an overview of the design of this framework and illustratethe simplicity of applying the available path sampling algorithms to a variety of benchmark problems.

Rare event simulation

2017 ◽  
Author(s):  
Michael P. Allen ◽  
Dominic J. Tildesley
Keyword(s):  
Rare Event ◽  
Path Sampling ◽  
Rapid Progress ◽  
Computationally Efficient ◽  
Transition Path ◽  
Transition Path Sampling ◽  
Event Simulation ◽  
Reaction Coordinates ◽  
Simulation Techniques ◽  
Transition Interface

The development of techniques to simulate infrequent events has been an area of rapid progress in recent years. In this chapter, we shall discuss some of the simulation techniques developed to study the dynamics of rare events. A basic summary of the statistical mechanics of barrier crossing is followed by a discussion of approaches based on the identification of reaction coordinates, and those which seek to avoid prior assumptions about the transition path. The demanding technique of transition path sampling is introduced and forward flux sampling and transition interface sampling are considered as rigorous but computationally efficient approaches.

scholarly journals Catalytic Mechanism of Processive GlfT2: Transition Path Sampling Investigation of Substrate Translocation

ACS Omega ◽  
2020 ◽  
Vol 5 (34) ◽  
pp. 21374-21384
Author(s):  
Pavel Janoš ◽  
Igor Tvaroška ◽  
Christoph Dellago ◽  
Jaroslav Koča
Keyword(s):  
Catalytic Mechanism ◽  
Path Sampling ◽  
Transition Path ◽  
Transition Path Sampling

Understanding rare safety and reliability events using transition path sampling

2018 ◽  
Vol 108 ◽  
pp. 74-88 ◽  
Author(s):  
Ian H. Moskowitz ◽  
Warren D. Seider ◽  
Amish J. Patel ◽  
Jeffrey E. Arbogast ◽  
Ulku G. Oktem
Keyword(s):  
Path Sampling ◽  
Transition Path ◽  
Transition Path Sampling ◽  
Safety And Reliability

scholarly journals Deciphering The Molecular Mechanism Of Water Boiling At Heterogeneous Interfaces

2021 ◽  
Author(s):  
Konstantinos Karalis ◽  
Dirk Zahn ◽  
Nikolaos Prasianakis ◽  
Bojan Niceno ◽  
Sergey V. Churakov
Keyword(s):  
Molecular Mechanism ◽  
Heat Removal ◽  
Nucleate Boiling ◽  
Surface Hydrophobicity ◽  
Bubble Nucleation ◽  
Geothermal Systems ◽  
Transition Path ◽  
Nucleation Sites ◽  
Dynamics Simulations ◽  
The Impact

Abstract Water boiling control evolution of natural geothermal systems is widely exploited in industrial processes due to the unique non-linear thermophysical behavior. Even though the properties of water both in the liquid and gas state have been extensively studied experimentally and by numerical simulations, there is still a fundamental knowledge gap in understanding the mechanism of the heterogeneous nucleate boiling controlling evaporation and condensation. In this study, the molecular mechanism of bubble nucleation at the hydrophilic and hydrophobic solid-water interface was determined by performing unbiased molecular dynamics simulations using the transition path sampling scheme. Analyzing the liquid to vapor transition path, the initiation of small void cavities (vapor bubbles nuclei) and their subsequent merging mechanism, leading to successively growing vacuum domains (vapor phase), has been elucidated. The molecular mechanism and the boiling nucleation sites' location are strongly dependent on the solid surface hydrophobicity and hydrophilicity. Then simulations reveal the impact of the surface functionality on the adsorbed thin water molecules film structuring and the location of high probability nucleation sites. Our findings provide molecular-scale insights into the computational aided design of new novel materials for more efficient heat removal and rationalizing the damage mechanisms.

scholarly journals Deciphering the molecular mechanism of water boiling at heterogeneous interfaces

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Konstantinos Karalis ◽  
Dirk Zahn ◽  
Nikolaos I. Prasianakis ◽  
Bojan Niceno ◽  
Sergey V. Churakov
Keyword(s):  
Molecular Mechanism ◽  
Heat Removal ◽  
Nucleate Boiling ◽  
Surface Hydrophobicity ◽  
Bubble Nucleation ◽  
Geothermal Systems ◽  
Transition Path ◽  
Nucleation Sites ◽  
Dynamics Simulations ◽  
The Impact

AbstractWater boiling control evolution of natural geothermal systems is widely exploited in industrial processes due to the unique non-linear thermophysical behavior. Even though the properties of water both in the liquid and gas state have been extensively studied experimentally and by numerical simulations, there is still a fundamental knowledge gap in understanding the mechanism of the heterogeneous nucleate boiling controlling evaporation and condensation. In this study, the molecular mechanism of bubble nucleation at the hydrophilic and hydrophobic solid–water interface was determined by performing unbiased molecular dynamics simulations using the transition path sampling scheme. Analyzing the liquid to vapor transition path, the initiation of small void cavities (vapor bubbles nuclei) and their subsequent merging mechanism, leading to successively growing vacuum domains (vapor phase), has been elucidated. The molecular mechanism and the boiling nucleation sites’ location are strongly dependent on the solid surface hydrophobicity and hydrophilicity. Then simulations reveal the impact of the surface functionality on the adsorbed thin water molecules film structuring and the location of high probability nucleation sites. Our findings provide molecular-scale insights into the computational aided design of new novel materials for more efficient heat removal and rationalizing the damage mechanisms.

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