scholarly journals Detailed Analysis of 17β-Estradiol-Aptamer InteractionsAptamer Interactions: A Molecular Dynamics Simulation Study

2018 ◽  
Author(s):  
Alexander Eisold ◽  
Dirk Labudde
Keyword(s):  
Md Simulation ◽  
3D Structure ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Negative Effects ◽  
Time Step ◽  
Binding Characteristics ◽  
Structure Information ◽  
Potential Binding ◽  
Interior Loop

Micro-pollutants such as 17β-Estradiol (E2) have been detected in different water resources and their negative effects on the environment and organisms have been observed. Aptamers are established as a possible detection tool, but the underlying ligand binding is largely unexplored. In this study, a previously described 35-mer E2-specific aptamer was used to analyse the binding characteristics between E2 and the aptamer with a MD simulation in an aqueous medium. Because there is no 3D structure information available for this aptamer, it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside a potential binding area of the predicted aptamer structure, the complex was used for an 25 ns MD simulation, and the interactions were examined for each time step. We identified E2-specific bases within the interior loop of the aptamer and also demonstrated the influence of frequently underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding with aptamer structure in an aqueous solution. The developed workflow allows generating and examining further appealing ligand-aptamer complexes.

scholarly journals Detailed Analysis of 17β-Estradiol-Aptamer Interactions – A Molecular Dynamics Simulation Study

2018 ◽  
Author(s):  
Alexander Eisold ◽  
Dirk Labudde
Keyword(s):  
Md Simulation ◽  
3D Structure ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Negative Effects ◽  
Time Step ◽  
Binding Characteristics ◽  
Structure Information ◽  
Low Concentrations ◽  
Interior Loop

Micro pollutants such as 17β-Estradiol (E2) have been detected in low concentrations in different water resources and their negative effects on the environment and organisms are observed. In this study, a previously described 35-mer E2-specific aptamer was used to investigate the underlying binding characteristics between E2 and the aptamer through an MD simulation in an aqueous medium. There is no 3D structure information for this aptamer, so it was modeled using coarse-grained modeling method. The E2 ligand was positioned inside the potential binding area of the aptamer structure, the underlying complex was used for an 25 ns MD simulation, and the interactions were examined by an interaction profiler tool for each time step. The E2-specific bases of the aptamer had presumably dominant roles in the binding of E2 in terms of the different interaction types. We identified the specific bases within the interior loop of the aptamer and we also demonstrate the influence of oftentimes underestimated water-mediated hydrogen bonds. The study contributes to the understanding of the behavior of ligands binding through aptamer structure in an aqueous solution. The developed workflow allows to generate and examine further appealing ligand aptamer complexes.

scholarly journals Solution structure of multi-domain protein ER-60 studied by aggregation-free SAXS and coarse-grained-MD simulation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Aya Okuda ◽  
Masahiro Shimizu ◽  
Ken Morishima ◽  
Rintaro Inoue ◽  
Nobuhiro Sato ◽  
...  
Keyword(s):  
Conformational Changes ◽  
Solution Structure ◽  
Md Simulation ◽  
Redox State ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
X Ray ◽  
Physiological Conditions ◽  
X Ray Scattering ◽  
Active Centres

AbstractMulti-domain proteins (MDPs) show a variety of domain conformations under physiological conditions, regulating their functions through such conformational changes. One of the typical MDPs, ER-60 which is a protein folding enzyme, has a U-shape with four domains and is thought to have different domain conformations in solution depending on the redox state at the active centres of the edge domains. In this work, an aggregation-free small-angle X-ray scattering revealed that the structures of oxidized and reduced ER-60 in solution are different from each other and are also different from those in the crystal. Furthermore, structural modelling with coarse-grained molecular dynamics simulation indicated that the distance between the two edge domains of oxidized ER-60 is longer than that of reduced ER-60. In addition, one of the edge domains has a more flexible conformation than the other.

scholarly journals Molecular dynamics lattice gas equilibrium distribution function for Lennard–Jones particles

2021 ◽  
Vol 379 (2208) ◽  
pp. 20200404 ◽  
Author(s):  
Aleksandra Pachalieva ◽  
Alexander J. Wagner
Keyword(s):  
Molecular Dynamics ◽  
Distribution Function ◽  
Lattice Boltzmann ◽  
Md Simulation ◽  
Lattice Gas ◽  
Equilibrium Distribution ◽  
Dynamics Simulation ◽  
Equilibrium Distribution Function ◽  
Weighted Sum ◽  
Time Step

The molecular dynamics lattice gas (MDLG) method maps a molecular dynamics (MD) simulation onto a lattice gas using a coarse-graining procedure. This is a novel fundamental approach to derive the lattice Boltzmann method (LBM) by taking a Boltzmann average over the MDLG. A key property of the LBM is the equilibrium distribution function, which was originally derived by assuming that the particle displacements in the MD simulation are Boltzmann distributed. However, we recently discovered that a single Gaussian distribution function is not sufficient to describe the particle displacements in a broad transition regime between free particles and particles undergoing many collisions in one time step. In a recent publication, we proposed a Poisson weighted sum of Gaussians which shows better agreement with the MD data. We derive a lattice Boltzmann equilibrium distribution function from the Poisson weighted sum of Gaussians model and compare it to a measured equilibrium distribution function from MD data and to an analytical approximation of the equilibrium distribution function from a single Gaussian probability distribution function. This article is part of the theme issue ‘Progress in mesoscale methods for fluid dynamics simulation’.

scholarly journals Heat diffusion-related damping process in a highly precise coarse-grained model for nonlinear motion of SWCNT

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Heeyuen Koh ◽  
Shohei Chiashi ◽  
Junichiro Shiomi ◽  
Shigeo Maruyama
Keyword(s):  
Molecular Dynamics ◽  
Memory Effect ◽  
Nonlinear Dynamic ◽  
Md Simulation ◽  
Internal Heat ◽  
Heat Diffusion ◽  
Coarse Grained ◽  
Good Precision ◽  
Time Step ◽  
Macroscopic Motion

AbstractSecond sound and heat diffusion in single-walled carbon nanotubes (SWCNT) are well-known phenomena which is related to the high thermal conductivity of this material. In this paper, we have shown that the heat diffusion along the tube axis affects the macroscopic motion of SWCNT and adapting this phenomena to coarse-grained (CG) model can improve the precision of the coarse-grained molecular dynamics (CGMD) exceptionally. The nonlinear macroscopic motion of SWCNT in the free thermal vibration condition in adiabatic environment is demonstrated in the most simplified version of CG modeling as maintaining finite temperature and total energy with suggested dissipation process derived from internal heat diffusion. The internal heat diffusion related to the cross correlated momentum from different potential energy functions is considered, and it can reproduce the nonlinear dynamic nature of SWCNTs without external thermostatting in CG model. Memory effect and thermostat with random noise distribution are not included, and the effect of heat diffusion on memory effect is quantified through Mori–Zwanzig formalism. This diffusion shows perfect syncronization of the motion between that of CGMD and MD simulation, which is started with initial conditions from the molecular dynamics (MD) simulation. The heat diffusion related to this process has shown the same dispersive characteristics to second wave in SWCNT. This replication with good precision indicates that the internal heat diffusion process is the essential cause of the nonlinearity of the tube. The nonlinear dynamic characteristics from the various scale of simple beads systems are examined with expanding its time step and node length.

scholarly journals Application of molecular dynamics simulation in self-assembly

2021 ◽  
Vol 2108 (1) ◽  
pp. 012085
Author(s):  
Mingjia Fang
Keyword(s):  
Force Field ◽  
Self Assembly ◽  
Md Simulation ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Practical Applications ◽  
The Past ◽  
Martini Force Field ◽  
Implicit And Explicit ◽  
The Way

Abstract During the past few years, numerous studies have been done in self-assembly. Among most of these studies, Molecular Dynamic Simulation is widely used to construct the experiment model. This work firstly introduced three practical applications of MD simulation in self-assembly. Then, two main kinds of simulation are discussed including all-atom simulation and coarse-grained simulation, together with the way of thoughts before the simulation start. It is found that researchers always start with the whole analysis of the substances that need to be studied. It helps to confirm the appropriate model that can apply in the simulation naturally. Besides, depended on the principles that need to be studied, the way of establishing the simulation system varies, ranging from separation experiment in both types of simulation to the change of essential parameters. Furthermore, the adoption of L-J potential in MD simulation proves to be a wise option on account of its convenient and simple model. It is remarkable that, considering some small details like the differences between implicit and explicit solution, classical Martini force field is replaced by Dry Martini force field.

scholarly journals Coarse-Grained Models Reveal Functional Dynamics – II. Molecular Dynamics Simulation at the Coarse-Grained Level – Theories and Biological Applications

2008 ◽  
Vol 2 ◽  
pp. BBI.S459 ◽  
Author(s):  
Choon-Peng Chng ◽  
Lee-Wei Yang
Keyword(s):  
Molecular Dynamics ◽  
Molecular Conformation ◽  
Conformational Dynamics ◽  
Dynamics Simulation ◽  
Coarse Grained ◽  
Time Step ◽  
Effective Potentials ◽  
Functional Dynamics ◽  
Indispensable Tool ◽  
Selection Of

Molecular dynamics (MD) simulation has remained the most indispensable tool in studying equilibrium/non-equilibrium conformational dynamics since its advent 30 years ago. With advances in spectroscopy accompanying solved biocomplexes in growing sizes, sampling their dynamics that occur at biologically interesting spatial/temporal scales becomes computationally intractable; this motivated the use of coarse-grained (CG) approaches. CG-MD models are used to study folding and conformational transitions in reduced resolution and can employ enlarged time steps due to the a bsence of some of the fastest motions in the system. The Boltzmann-Inversion technique, heavily used in parameterizing these models, provides a smoothed-out effective potential on which molecular conformation evolves at a faster pace thus stretching simulations into tens of microseconds. As a result, a complete catalytic cycle of HIV-1 protease or the assembly of lipid-protein mixtures could be investigated by CG-MD to gain biological insights. In this review, we survey the theories developed in recent years, which are categorized into Folding-based and Molecular-Mechanics-based. In addition, physical bases in the selection of CG beads/time-step, the choice of effective potentials, representation of solvent, and restoration of molecular representations back to their atomic details are systematically discussed.

scholarly journals Probing the Structural Basis of Citrus Phytochrome B using Computational Modelling and Molecular Dynamics Simulation Approaches

2021 ◽  
Author(s):  
Muhammad Tahir ul Qamar ◽  
Muhammad Usman Mirza ◽  
Jia-Ming Song ◽  
Muhammad Junaid Rao ◽  
Xi-Tong Zhu ◽  
...  
Keyword(s):  
Md Simulation ◽  
Red Light ◽  
3D Structure ◽  
Computational Modelling ◽  
Structural Difference ◽  
Dynamics Simulation ◽  
Structural Basis ◽  
Functional Implications ◽  
Domain Organisation ◽  
Photosynthetic Potential

Phytochromes are known as red/far-red light photoreceptors and responsible for directing the photosensory responses across the species. Such responses majorly include photosynthetic potential and pigmentation in bacteria, whereas in a plant, they are involved in chloroplast development and photomorphogenesis. Many prokaryotic Phys have been modelled for their structural/functional analysis, but their plant counterparts have not been explored yet. To date, only the crystal structures of the photo-sensing module of PhyB isoform from Arabidopsis and Glycine have been resolved experimentally. Thus, in this study, we elucidated the complete 3D structure of Citrus PhyB. Initially, the structure and organisation of the Citrus PhyB have been predicted computationally, which were found to have the same domain organisation as A.thaliana and G.max PhyBs, yet their considerable distinct structural difference indicated potential divergence in signaling/functioning. Therefore, to evaluate the structural and functional implications of Citrus PhyB, we compared its structure with A. thaliana and G. max PhyBs using MD simulation. The modeling studies revealed that the region of Citrus PhyB-GAF domain possibly contributes to the variations. Hence, structural/molecular insights into Citrus PhyB can help to discover the Phys signaling and thus, an essential framework can be designed for optogenetic reagents and various agricultural benefits.

MODELING OF THREE DIMENSIONAL STRUCTURE OF HUMAN ALPHA-FETOPROTEIN COMPLEXED WITH DIETHYLSTILBESTROL: DOCKING AND MOLECULAR DYNAMICS SIMULATION STUDY

2012 ◽  
Vol 10 (02) ◽  
pp. 1241012 ◽  
Author(s):  
ALEXANDER A. TERENTIEV ◽  
NURBUBU T. MOLDOGAZIEVA ◽  
OLGA V. LEVTSOVA ◽  
DMITRY M. MAXIMENKO ◽  
DENIS A. BOROZDENKO ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Binding Site ◽  
Simulation Study ◽  
Md Simulation ◽  
Hydrophobic Interactions ◽  
3D Structure ◽  
Three Dimensional ◽  
Alpha Fetoprotein ◽  
Dynamics Simulation ◽  
Dimensional Structure

It has been long experimentally demonstrated that human alpha-fetoprotein (HAFP) has an ability to bind immobilized estrogens with the most efficiency for synthetic estrogen analog — diethylstilbestrol (DES). However, the question remains why the human AFP (HAFP), unlike rodent AFP, cannot bind free estrogens. Moreover, despite the fact that AFP was first discovered more than 50 years ago and is presently recognized as a "golden standard" among onco-biomarkers, its three-dimensional (3D) structure has not been experimentally solved yet. In this work using MODELLER program, we generated 3D model of HAFP on the basis of homology with human serum albumin (HSA) and Vitamin D–binding protein (VTDB) with subsequent molecular docking of DES to the model structure and molecular dynamics (MD) simulation study of the complex obtained. The model constructed has U-shaped structure in which a cavity may be distinguished. In this cavity the putative estrogen-binding site is localized. Validation by RMSD calculation and with the use of PROCHECK program showed good quality of the model and stability of extended region of four alpha-helical structures that contains putative hormone-binding residues. Data extracted from MD simulation trajectory allow proposing two types of interactions between amino acid residues of HAFP and DES molecule: (1) hydrogen bonding with involvement of residues S445, R452, and E551; (2) hydrophobic interactions with participation of L138, M448, and M548 residues. A suggestion is made that immobilization of the hormone using a long spacer provides delivery of the estrogen molecule to the binding site and, thereby, facilitates interaction between HAFP and the hormone.

Molecular Dynamics Simulation With Interval-Valued Interatomic Potentials

2016 ◽  
Author(s):  
Anh Tran ◽  
Yan Wang
Keyword(s):  
Molecular Dynamics ◽  
Md Simulation ◽  
Interatomic Potential ◽  
Thermal Fluctuation ◽  
Potential Functions ◽  
Dynamics Simulation ◽  
Computational Time ◽  
System Control ◽  
Interatomic Potentials ◽  
Time Step

In molecular dynamics (MD) simulation, the two main sources of uncertainty are the interatomic potential functions and thermal fluctuation. The accuracy of the interatomic potential functions plays a vital role toward the reliability of MD simulation prediction. Reliable molecular dynamics (R-MD) is an interval-based MD simulation platform, where atomistic positions and velocities are represented as Kaucher (or generalized) intervals to capture the uncertainty associated with the inter-atomic potentials. The advantage of this uncertainty quantification (UQ) approach is that the uncertainty effect can be assessed on-the-fly with only one run of simulation, and thus the computational time for UQ is significantly reduced. In this paper, an extended interval statistical ensemble is introduced to quantify the uncertainty associated with the system control variables, such as temperature and pressure at each time-step. This method allows for quantifying and propagating the uncertainty in the system as MD simulation advances. An example of interval isothermal-isobaric (NPT) ensemble is implemented to demonstrate the feasibility of applying the intrusive UQ technique toward MD simulation.

Structural Insights into the IL12:IL12 Receptor Complex Assembly by Molecular Modeling, Docking, and Molecular Dynamics Simulation

2020 ◽  
Vol 23 ◽  
Author(s):  
Sakshi Singh ◽  
Geeta Rai
Keyword(s):  
Structure Prediction ◽  
Md Simulation ◽  
De Novo ◽  
3D Structure ◽  
Computational Method ◽  
Dynamics Simulation ◽  
Hematopoietic Progenitor Cell ◽  
Interleukin 12 ◽  
Type I ◽  
Progenitor Cell Proliferation

Background: Interleukin-12 receptor (IL12R) is a type I cytokine receptor that can promote hematopoiesis and regulate innate and adaptive immunity. It binds with the IL12 ligand, which activates the IL-12 signaling pathway that triggers hematopoietic progenitor cell proliferation and differentiation process. The structure of IL12:IL12R complex is not known. Objective: The present work describes a de novo computational method for rational protein designing to elucidate the structure of IL12:IL12R complex. Methods: Homology modeling, docking, and MD simulation methods were used to design mimics of the interaction of IL12 and IL12R. Results: 3D structure prediction and validation confirms the accurate structure of IL12R protein that contains immunoglobin domain, fibronectin type three domain, cytokine-binding domain, and WSXWS motif. Molecular docking and MD simulation revealed that IL12R bound tightly with IL12 ligand at their interface. The estimated binding energy of the docked complex was -26.7 kcal/mol, and the interface area was 281.4 Å2. Hotspot prediction suggested that ARG34, SER58, GLU61, CYS62, LEU63, SER73, ASP142, GLN146, LYS168, THR169 ARG181, ARG183, ARG189, and TYR193 residues in IL12 ligand interacted with SER175, ALA176, CYS177, PRO178, ALA179, ALA180, GLU181, GLU182, ALA192, VAL193, HIS194, ARG208, TYR246, GLN289, ASP290, ARG291, TYR292, TYR293 and SER294 residues in IL12 receptor. Conclusion: The results of the study provides a simulated molecular structure of IL12:IL12R complex that could offer a promising target complex to substantiate IL12 based drug-designing approaches.

Sign in / Sign up

Export Citation Format

Share Document