scholarly journals Implementation of Geometry Dependent Charge Flux into Polarizable AMOEBA+ Potential

2019 ◽  
Author(s):  
Chengwen Liu ◽  
Jean-Philip Piquemal ◽  
Pengyu Ren
Keyword(s):  
Molecular Dynamics ◽  
Atomic Charge ◽  
Md Simulations ◽  
Water Model ◽  
Local Geometry ◽  
Important Ingredient ◽  
Binding Interaction ◽  
Molecular Systems ◽  
Water Models ◽  
Charge Flux

Molecular dynamics (MD) simulations employing classical force fields (FFs) have been widely used to model molecular systems. The important ingredient of the current FFs, atomic charge, remains fixed during MD simulations despite the atomic environment or local geometry changes. This approximation hinders the transferability of the potential being used in multiple phases. Here we implement a geometry dependent charge flux (GDCF) model into the multipole-based AMOEBA+ polarizable potential. The CF in the current work explicitly depends on the local geometry (<i>bond and angle</i>) of the molecule. To our knowledge, this is the first study that derives energy and force expressions due to GDCF in a multipole-based polarizable FF framework. Due to the inclusion of GDCF, the AMOEBA+ water model is noticeably improved in terms of describing the monomer properties, cluster binding/interaction energy and a variety of liquid properties, including the infrared spectra that previous flexible water models were not able to capture.

scholarly journals Implementation of Geometry Dependent Charge Flux into Polarizable AMOEBA+ Potential

2019 ◽  
Author(s):  
Chengwen Liu ◽  
Jean-Philip Piquemal ◽  
Pengyu Ren
Keyword(s):  
Molecular Dynamics ◽  
Atomic Charge ◽  
Md Simulations ◽  
Water Model ◽  
Local Geometry ◽  
Important Ingredient ◽  
Binding Interaction ◽  
Molecular Systems ◽  
Water Models ◽  
Charge Flux

Molecular dynamics (MD) simulations employing classical force fields (FFs) have been widely used to model molecular systems. The important ingredient of the current FFs, atomic charge, remains fixed during MD simulations despite the atomic environment or local geometry changes. This approximation hinders the transferability of the potential being used in multiple phases. Here we implement a geometry dependent charge flux (GDCF) model into the multipole-based AMOEBA+ polarizable potential. The CF in the current work explicitly depends on the local geometry (<i>bond and angle</i>) of the molecule. To our knowledge, this is the first study that derives energy and force expressions due to GDCF in a multipole-based polarizable FF framework. Due to the inclusion of GDCF, the AMOEBA+ water model is noticeably improved in terms of describing the monomer properties, cluster binding/interaction energy and a variety of liquid properties, including the infrared spectra that previous flexible water models were not able to capture.

scholarly journals QM/MM Molecular Dynamics Investigation of the Binding of Organic Phosphates to the 100 Diaspore Surface

2020 ◽  
Author(s):  
Prasanth Babu Ganta ◽  
Oliver Kühn ◽  
Ashour Ahmed
Keyword(s):  
Molecular Dynamics ◽  
Food System ◽  
Specific Binding ◽  
Md Simulations ◽  
Mineral Surfaces ◽  
Soil Mineral ◽  
Molecular Systems ◽  
Organic Phosphates ◽  
Surface Plane

<div><div><div><p>The fate of phosphorus (P) in the eco-system is strongly affected by the interaction of phos- phates with soil components and especially reactive soil mineral surfaces. As a consequence, P immobilization could occur which eventually leads to P inefficiency and thus unavailability to plants with strong implications on the global food system. A molecular level understanding of the mechanisms of the P binding to soil mineral surfaces could be a key for the development of novel strategies for more efficient P application. Much experimental work has been done to understand P binding to several reactive and abundant minerals especially goethite (α-FeOOH). On the other hand, atomistic modeling of the P-mineral molecular systems using molecular dynamics (MD) simulations is emerging as a new tool which provides more detailed information regarding the mechanisms, nature, and strength of these binding processes. The present study characterize the binding of the most abundant organic phosphates in forest soils, inositol hexaphosphate (IHP) and glycerolphosphate (GP), to the 100 diaspore (α-AlOOH) surface plane. Here, different molecular models have been introduced to simulate typical situations for the P-binding at the diaspore/water interface. For all models, quantum mechanics/molecular mechanics (QM/MM) based MD simulations have been performed to explore the diaspore–IHP/GP–water interactions. The results provide evidence for the formation of monodentate (M) and bidentate (B) motifs for GP and M and as well as two monodentate (2M) motifs for IHP with the surface. The calculated interaction energies suggest that GP and IHP prefer to form the B and 2M motif, respectively. Moreover, IHP exhibited stronger binding than GP with diaspore and water. Further, the role of water in controlling binding strengths via promoting of specific binding motifs, formation of H-bonds, adsorption and dissociation at the surface, as well as proton transfer processes is demonstrated. Finally, the P-binding at the 100 diaspore surface plane is weaker than that at the 010 plane highlighting the influential role of the coordination number of Al atoms at the top surface of diaspore.</p></div></div></div>

scholarly journals Stability of Two-quartet G-quadruplexes and Their Dimers in Atomistic Simulations

2019 ◽  
Author(s):  
Barira Islam ◽  
Petr Stadlbauer ◽  
Michaela Vorlíčková ◽  
Jean-Louis Mergny ◽  
Michal Otyepka ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Md Simulations ◽  
The Other ◽  
Atomistic Simulations ◽  
Structural Element ◽  
Dna And Rna ◽  
Open Issue ◽  
Water Models ◽  
Weakly Stable ◽  
The Stability

ABSTRACTG-quadruplexes (GQs) are four-stranded non-canonical DNA and RNA architectures that can be formed by guanine-rich sequences. The stability of GQs increases with the number of G-quartets and three G-quartets generally form stable GQs. However, the stability of two-quartet GQs is an open issue. To understand the intrinsic stability of two-quartet GQ stems, we have carried out a series of unbiased molecular dynamics (MD) simulations (∼505 µs in total) of two- and four-quartet DNA and RNA GQs, with attention paid mainly to parallel-stranded arrangements. We used AMBER DNA parmOL15 and RNA parmOL3 force fields and tested different ion and water models. DNA two-quartet parallel-stranded GQs unfolded in all the simulations while the equivalent RNA GQ was stable in most of the simulations. GQs composed of two stacked units of two-quartet GQs were stable for both DNA and RNA. The simulations suggest that a minimum of three quartets are needed to form an intrinsically stable all-anti parallel-stranded DNA GQ. Parallel two-quartet DNA GQ may exist if substantially stabilized by another molecule or structural element, including multimerisation. On the other hand, we predict that isolated RNA two-quartet parallel GQs may form, albeit being weakly stable. We also show that ionic parameters and water models should be chosen with caution because some parameter combinations can cause spurious instability of GQ stems. Some in-so-far unnoticed limitations of force-field description of multiple ions inside the GQs are discussed, which compromise capability of simulations to fully capture the effect of increase of the number of quartets on the GQ stability.

scholarly journals Development of Charge-Augmented Three-Point Water Model (CAIPi3P) for Accurate Simulations of Intrinsically Disordered Proteins

2019 ◽  
Author(s):  
Joao Victor de Souza Cunha ◽  
Francesc Sabanes Zariquiey ◽  
Agnieszka K. Bronowska
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Intrinsically Disordered Proteins ◽  
Md Simulations ◽  
Disordered Proteins ◽  
Water Model ◽  
High Plasticity ◽  
Solvation Model ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

Intrinsically disordered proteins (IDPs) are molecules without a fixed tertiary structure, exerting crucial roles in cellular signalling, growth and molecular recognition events. Due to their high plasticity, IDPs are very challenging in experimental and computational structural studies. To provide detailed atomic insight in IDPs dynamics governing its functional mechanisms, all-atom molecular dynamics (MD) simulations are widely employed. However, the current generalist force fields and solvent models are unable to generate satisfactory ensembles for IDPs when compared to existing experimental data. In this work, we present a new solvation model, denoted as Charge-Augmented 3 Point Water model for Intrinsically-disordered Proteins (CAIPi3P). CAIPi3P has been generated by performing a systematic scanning of atomic partial charges assigned to the widely popular molecular scaffold of the three-point TIP3P water model. We found that explicit solvent MD simulations employing CAIPi3P solvation considerably improved the SAXS scattering profiles for three different IDPs. Not surprisingly, this improvement was further enhanced by using CAIPi3P water in combination with the protein force field parametrized for IDPs. We have also demonstrated applicability of CAIPi3P to molecular systems containing structured as well as intrinsically disordered regions/domains. Our results highlight the crucial importance of solvent effects for generating molecular ensembles of IDPs which reproduce the experimental data available. Hence, we conclude that our newly developed CAIPi3P solvation model is a valuable tool assisting molecular simulations of intrinsically disordered proteins and assessing their molecular dynamics.

scholarly journals Development of Charge-Augmented Three-Point Water Model (CAIPi3P) for Accurate Simulations of Intrinsically Disordered Proteins

2020 ◽  
Vol 21 (17) ◽  
pp. 6166
Author(s):  
Joao V. de Souza ◽  
Francesc Sabanés Zariquiey ◽  
Agnieszka K. Bronowska
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Intrinsically Disordered Proteins ◽  
Md Simulations ◽  
Disordered Proteins ◽  
Water Model ◽  
High Plasticity ◽  
Solvation Model ◽  
Intrinsically Disordered ◽  
Intrinsically Disordered Regions

Intrinsically disordered proteins (IDPs) are molecules without a fixed tertiary structure, exerting crucial roles in cellular signalling, growth and molecular recognition events. Due to their high plasticity, IDPs are very challenging in experimental and computational structural studies. To provide detailed atomic insight in IDPs’ dynamics governing their functional mechanisms, all-atom molecular dynamics (MD) simulations are widely employed. However, the current generalist force fields and solvent models are unable to generate satisfactory ensembles for IDPs when compared to existing experimental data. In this work, we present a new solvation model, denoted as the Charge-Augmented Three-Point Water Model for Intrinsically Disordered Proteins (CAIPi3P). CAIPi3P has been generated by performing a systematic scan of atomic partial charges assigned to the widely popular molecular scaffold of the three-point TIP3P water model. We found that explicit solvent MD simulations employing CAIPi3P solvation considerably improved the small-angle X-ray scattering (SAXS) scattering profiles for three different IDPs. Not surprisingly, this improvement was further enhanced by using CAIPi3P water in combination with the protein force field parametrized for IDPs. We also demonstrated the applicability of CAIPi3P to molecular systems containing structured as well as intrinsically disordered regions/domains. Our results highlight the crucial importance of solvent effects for generating molecular ensembles of IDPs which reproduce the experimental data available. Hence, we conclude that our newly developed CAIPi3P solvation model is a valuable tool for molecular simulations of intrinsically disordered proteins and assessing their molecular dynamics.

scholarly journals DDT - Drug Discovery Tool: a fast and intuitive graphics user interface for docking and molecular dynamics analysis

2019 ◽  
Author(s):  
Simone Aureli ◽  
Daniele Di Marino ◽  
Stefano Raniolo ◽  
Vittorio Limongelli
Keyword(s):  
Molecular Dynamics ◽  
User Interface ◽  
Drug Discovery ◽  
Protein Binding ◽  
Protein Complexes ◽  
Md Simulations ◽  
Supplementary Information ◽  
Chemical Information ◽  
Binding Interaction ◽  
Fast Analysis

Abstract Motivation The ligand/protein binding interaction is typically investigated by docking and molecular dynamics (MD) simulations. In particular, docking-based virtual screening (VS) is used to select the best ligands from database of thousands of compounds, while MD calculations assess the energy stability of the ligand/protein binding complexes. Considering the broad use of these techniques, it is of great demand to have one single software that allows a combined and fast analysis of VS and MD results. With this in mind, we have developed the Drug Discovery Tool (DDT) that is an intuitive graphics user interface able to provide structural data and physico-chemical information on the ligand/protein interaction. Results DDT is designed as a plugin for the Visual Molecular Dynamics (VMD) software and is able to manage a large number of ligand/protein complexes obtained from AutoDock4 (AD4) docking calculations and MD simulations. DDT delivers four main outcomes: i) ligands ranking based on an energy score; ii) ligand ranking based on a ligands’ conformation cluster analysis; iii) identification of the aminoacids forming the most occurrent interactions with the ligands; iv) plot of the ligands’ center-of-mass coordinates in the Cartesian space. The flexibility of the software allows saving the best ligand/protein complexes using a number of user-defined options. Availability and implementation DDT_site_1 (alternative DDT_site_2); the DDT tutorial movie is available here. Supplementary information Supplementary data are available at Bioinformatics online.

Hydrophobicity of an isobutane dimer in water, methanol and acetonitrile as solvents — A classical molecular dynamics study

2019 ◽  
Vol 33 (32) ◽  
pp. 1950391
Author(s):  
Sailesh Bataju ◽  
Nurapati Pantha
Keyword(s):  
Molecular Dynamics ◽  
Coordination Number ◽  
Center Of Mass ◽  
Sampling Technique ◽  
Md Simulations ◽  
Solvation Shell ◽  
Umbrella Sampling ◽  
Water Model ◽  
Solvent Environment ◽  
Potential Of Mean Forces

The potential of mean forces (PMFs) has been determined for an isobutane dimer in various solvent environments such as water, methanol and acetonitrile at a temperature of 298 K and pressure of 1 bar using GROMACS software. All the molecular dynamics (MD) simulations are carried out using a TIP3P water model under a CHARMM36 forcefield. Following Umbrella Sampling technique, PMFs are calculated and analyzed using Weighted Histogram Analysis Method (WHAM) and coordination number of first solvation shell is extracted for all solvents using radial distribution function. The shape of PMFs contains contact minima, solvent-separated minima and desolvation maxima. The values of contact minima are not affected much by solvent environment and found to be at 0.5377, 0.5480 and 0.5495 nm for water, methanol and acetonitrile respectively. The corresponding energy depths are found −0.9134, −0.7080 and −0.5295 kcalmol[Formula: see text]. The variation observed at solvent-separated minima is noticeable and found at 0.9012, 0.9721 and 0.9151 nm for water, methanol and acetonitrile, respectively. The coordination number of the first solvation shell by taking an isobutane molecule as a reference from their center of mass is found to be 28.1, 16.9 and 14.8 for water, methanol and acetonitrile, respectively. There is a soft hydrophobic interaction between isobutane dimer and solvents like methanol and acetonitrile relative to water, might be due to the presence of competitive methyl group of methanol and acetonitrile in the solvent medium.

scholarly journals Accurate Simulations of Lipid Monolayers Require a Water Model With Correct Surface Tension

2021 ◽  
Author(s):  
Carmelo Tempra ◽  
O.H. Samuli Ollila ◽  
Matti Javanainen
Keyword(s):  
Molecular Dynamics ◽  
Surface Tension ◽  
Molecular Dynamics Simulations ◽  
Long Range ◽  
Van Der Waals ◽  
Water Model ◽  
Lipid Monolayers ◽  
Experimental Surface ◽  
Water Models ◽  
Dynamics Simulations

Lipid monolayers provide our lungs and eyes their functionality, and serve as proxy systems in biomembrane research. Therefore, lipid monolayers have been studied intensively also using molecular dynamics simulations, which are able to probe their lateral structure and interactions with, e.g., pharmaceuticals or nanoparticles. However, such simulations have struggled in describing the forces at the air–water interface. Particularly the surface tension of water and long-range van der Waals interactions have been considered critical, but their importance in monolayer simulations has been evaluated only separately. Here we combine the recent C36/LJ-PME lipid force field that in- cludes long-range van der Waals forces with water models that reproduce experimental surface tensions to elucidate the importance of these contributions in monolayer simulations. Our results suggest that a water model with correct surface tension is necessary to reproduce experimental surface pressure–area isotherms and monolayer phase behavior, while standard cutoff-based CHARMM36 lipid model with the 4-point OPC water model still provides the best agreement with experiments. Our results emphasize the importance of using high quality water models in applications and parameter development in molecular dynamics simulations of biomolecules.

scholarly journals Investigating an Efficient and Accurate Protocol for Sampling Structures from Molecular Dynamics Simulations: A Close Look by Different Wavelet Families

2021 ◽  
Author(s):  
Mateus Gonçalves ◽  
Arismar Junior ◽  
Elaine da Cunha ◽  
Teodorico Ramalho
Keyword(s):  
Experimental Data ◽  
Molecular Dynamics ◽  
Md Simulations ◽  
Quantum Calculations ◽  
Sampling Protocol ◽  
Molecular Systems ◽  
Electronic Parameters ◽  
Dynamics Simulations ◽  
Over Time ◽  
Wavelet Family

Molecular Dynamics (MD) simulations are widely used to predict the behavior of molecular systems over time. However, one of the great challenges of MD simulations is how to treat the thousands of configurations obtained from calculations, since the number of the quantum calculations (QM) required for evaluating electronic parameters is too high and, sometimes, computationally impracticable. Thus, an efficient and accurate sampling protocol is essential for combining classical MD and QM calculations. In this article, based on the OWSCA methodology, 93 wavelet signals were analyzed in order to further refine the methodology and identify the best wavelet family for [Fe(H2O)6]2+ and [Mn(H2O)6]2+ complexes in solution. Our results point out that the bior1.3 was the best wavelet, values closest to the experimental data were obtained for both studied systems.

scholarly journals QM/MM Molecular Dynamics Investigation of the Binding of Organic Phosphates to the 100 Diaspore Surface

2019 ◽  
Author(s):  
Prasanth Babu Ganta ◽  
Oliver Kühn ◽  
Ashour Ahmed
Keyword(s):  
Molecular Dynamics ◽  
Food System ◽  
Specific Binding ◽  
Md Simulations ◽  
Mineral Surfaces ◽  
Soil Mineral ◽  
Molecular Systems ◽  
Organic Phosphates ◽  
Surface Plane

<div><div><div><p>The fate of phosphorus (P) in the eco-system is strongly affected by the interaction of phos- phates with soil components and especially reactive soil mineral surfaces. As a consequence, P immobilization could occur which eventually leads to P inefficiency and thus unavailability to plants with strong implications on the global food system. A molecular level understanding of the mechanisms of the P binding to soil mineral surfaces could be a key for the development of novel strategies for more efficient P application. Much experimental work has been done to understand P binding to several reactive and abundant minerals especially goethite (α-FeOOH). On the other hand, atomistic modeling of the P-mineral molecular systems using molecular dynamics (MD) simulations is emerging as a new tool which provides more detailed information regarding the mechanisms, nature, and strength of these binding processes. The present study characterize the binding of the most abundant organic phosphates in forest soils, inositol hexaphosphate (IHP) and glycerolphosphate (GP), to the 100 diaspore (α-AlOOH) surface plane. Here, different molecular models have been introduced to simulate typical situations for the P-binding at the diaspore/water interface. For all models, quantum mechanics/molecular mechanics (QM/MM) based MD simulations have been performed to explore the diaspore–IHP/GP–water interactions. The results provide evidence for the formation of monodentate (M) and bidentate (B) motifs for GP and M and as well as two monodentate (2M) motifs for IHP with the surface. The calculated interaction energies suggest that GP and IHP prefer to form the B and 2M motif, respectively. Moreover, IHP exhibited stronger binding than GP with diaspore and water. Further, the role of water in controlling binding strengths via promoting of specific binding motifs, formation of H-bonds, adsorption and dissociation at the surface, as well as proton transfer processes is demonstrated. Finally, the P-binding at the 100 diaspore surface plane is weaker than that at the 010 plane highlighting the influential role of the coordination number of Al atoms at the top surface of diaspore.</p></div></div></div>

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