scholarly journals A variational approach to nucleation simulation

2016 ◽  
Vol 195 ◽  
pp. 557-568 ◽  
Author(s):  
Pablo M. Piaggi ◽  
Omar Valsson ◽  
Michele Parrinello
Keyword(s):  
Molecular Dynamics ◽  
Computer Simulation ◽  
Free Energy ◽  
Variational Approach ◽  
Sampling Method ◽  
Enhanced Sampling ◽  
Technical Problems ◽  
Lennard Jones ◽  
Dynamics Simulations

We study by computer simulation the nucleation of a supersaturated Lennard-Jones vapor into the liquid phase. The large free energy barriers to transition make the time scale of this process impossible to study by ordinary molecular dynamics simulations. Therefore we use a recently developed enhanced sampling method [Valsson and Parrinello, Phys. Rev. Lett.113, 090601 (2014)] based on the variational determination of a bias potential. We differ from previous applications of this method in that the bias is constructed on the basis of the physical model provided by the classical theory of nucleation. We examine the technical problems associated with this approach. Our results are very satisfactory and will pave the way for calculating the nucleation rates in many systems.

scholarly journals Ring Puckering Landscapes of Glycosaminoglycan-Related Monosaccharides from Molecular Dynamics Simulations

2019 ◽  
Author(s):  
Irfan Alibay ◽  
Richard Bryce
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Biological Function ◽  
Enhanced Sampling ◽  
Energy Profiles ◽  
Ring Puckering ◽  
Dynamics Simulations ◽  
Ring Pucker ◽  
Free Energy Profiles

<p>The conformational flexibility of the glycosaminoglycans (GAGs) are known to be key in their binding and biological function, for example in regulating coagulation and cell growth. In this work, we employ enhanced sampling molecular dynamics simulations to probe the ring conformations of GAG-related monosaccharides, including a range of acetylated and sulfated GAG residues. We first perform unbiased MD simulations of glucose anomers and the epimers glucoronate and iduronate. These calculations indicate that in some cases, an excess of 15 microseconds are required for adequate sampling of ring pucker due to the high energy barriers between states. However, by applying our recently developed msesMD simulation method (multidimensional swarm enhanced sampling molecular dynamics), we were able to quantitatively and rapidly reproduce these ring pucker landscapes. From msesMD simulations, the puckering free energy profiles were then compared for eleven monosaccharides found in GAGs; this includes to our knowledge the first simulation study of sulfation effects on GalNAc ring puckering. For the force field employed, we find that in general the calculated pucker free energy profiles for sulfated sugars were similar to the corresponding unsulfated profiles. This accords with recent experimental studies suggesting that variation in ring pucker of sulfated GAG residues is primarily dictated by interactions with surrounding residues rather than by intrinsic conformational preference. As an exception to this, however, we predict that 4-O-sulfation of GalNAc leads to reduced ring rigidity, with a significant lowering in energy of the <sup>1</sup>C<sub>4</sub> ring conformation; this observation may have implications for understanding the structural basis of the biological function of GalNAc-containing glycosaminoglycans such as dermatan sulfate.</p>

scholarly journals Effective Determination of Coexistence Curves using Reversible-Scaling Molecular Dynamics Simulations

2000 ◽  
Vol 653 ◽  
Author(s):  
Maurice de Koning ◽  
Alex Antonelli ◽  
Sidney Yip
Keyword(s):  
Molecular Dynamics ◽  
Md Simulation ◽  
Melting Curve ◽  
Coexistence Curve ◽  
Nonequilibrium Molecular Dynamics ◽  
Computational Cell ◽  
Clapeyron Equation ◽  
Lennard Jones ◽  
Dynamics Simulations

AbstractWe present a simulation technique that allows the calculation of a phase coexistence curve from a single nonequilibrium molecular dynamics (MD) simulation. The approach is based on the simultaneous simulation of two coexisting phases, each in its own computational cell, and the integration of the relevant Clausius-Clapeyron equation starting from a known coexistence point. As an illustration of the effectiveness of our approach we apply the method to explore the melting curve in the Lennard-Jones phase diagram.

scholarly journals Ring Puckering Landscapes of Glycosaminoglycan-Related Monosaccharides from Molecular Dynamics Simulations

2019 ◽  
Author(s):  
Irfan Alibay ◽  
Richard Bryce
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Biological Function ◽  
Enhanced Sampling ◽  
Energy Profiles ◽  
Ring Puckering ◽  
Dynamics Simulations ◽  
Ring Pucker ◽  
Free Energy Profiles

<p>The conformational flexibility of the glycosaminoglycans (GAGs) are known to be key in their binding and biological function, for example in regulating coagulation and cell growth. In this work, we employ enhanced sampling molecular dynamics simulations to probe the ring conformations of GAG-related monosaccharides, including a range of acetylated and sulfated GAG residues. We first perform unbiased MD simulations of glucose anomers and the epimers glucoronate and iduronate. These calculations indicate that in some cases, an excess of 15 microseconds are required for adequate sampling of ring pucker due to the high energy barriers between states. However, by applying our recently developed msesMD simulation method (multidimensional swarm enhanced sampling molecular dynamics), we were able to quantitatively and rapidly reproduce these ring pucker landscapes. From msesMD simulations, the puckering free energy profiles were then compared for eleven monosaccharides found in GAGs; this includes to our knowledge the first simulation study of sulfation effects on GalNAc ring puckering. For the force field employed, we find that in general the calculated pucker free energy profiles for sulfated sugars were similar to the corresponding unsulfated profiles. This accords with recent experimental studies suggesting that variation in ring pucker of sulfated GAG residues is primarily dictated by interactions with surrounding residues rather than by intrinsic conformational preference. As an exception to this, however, we predict that 4-O-sulfation of GalNAc leads to reduced ring rigidity, with a significant lowering in energy of the <sup>1</sup>C<sub>4</sub> ring conformation; this observation may have implications for understanding the structural basis of the biological function of GalNAc-containing glycosaminoglycans such as dermatan sulfate.</p>

scholarly journals Accelerating Dissociative Events in Molecular Dynamics Simulations by Selective Potential Scaling

2019 ◽  
Author(s):  
Indrajit Deb ◽  
Aaron T. Frank
Keyword(s):  
Molecular Dynamics ◽  
Sampling Method ◽  
Potential Energy Function ◽  
Md Simulations ◽  
Cyclin Dependent Kinase ◽  
Enhanced Sampling ◽  
Free Energies ◽  
Biologically Relevant ◽  
Dynamics Simulations ◽  
Dissociative Processes

ABSTRACTMolecular dynamics (or MD) simulations can be a powerful tool for modeling complex dissociative processes such as ligand unbinding. However, many biologically relevant dissociative processes occur on timescales that far exceed the timescales of typical MD simulations. Here, we implement and apply an enhanced sampling method in which specific energy terms in the potential energy function are selectively “scaled” to accelerate dissociative events during simulations. Using ligand unbinding as an example of a complex dissociative process, we selectively scaled-up ligand-water interactions in an attempt to increase the rate of ligand unbinding. By applying our selectively scaled MD (or ssMD) approach to three cyclin-dependent kinase 2 (CDK2)-inhibitor complexes, we were able to significantly accelerate ligand unbinding thereby allowing, in some cases, unbinding events to occur within as little as 2 ns. Moreover, we found that we could make realistic estimates of the unbinding as well as the binding free energies (∆Gsim) of the three inhibitors from our ssMD simulation data. To accomplish this, we employed a previously described Kramers’-based rate extrapolation (KRE) method and a newly described free energy extrapolation (FEE) method. Because our ssMD approach is general, it should find utility as an easy-to-deploy, enhanced sampling method for modeling other dissociative processes.

Determination of Interphase Thickness and Mechanical Properties of Effective Nanofillers in Polymer Nanocomposites by Molecular Dynamic Simulation

2010 ◽  
Vol 654-656 ◽  
pp. 1654-1657 ◽  
Author(s):  
Wen Xu ◽  
Qing Hua Zeng ◽  
Ai Bing Yu ◽  
Donald R. Paul
Keyword(s):  
Mechanical Properties ◽  
Molecular Dynamics ◽  
Computer Simulation ◽  
Polymer Nanocomposites ◽  
Polymer Materials ◽  
Reinforced Composites ◽  
Physical Size ◽  
And Performance ◽  
Dynamics Simulations

The properties of interphase in polymer composites are often different from those of bulk polymer matrix, which may include chemical, physical, microstructural, and mechanical properties. The nature of interphase is critical to the overall properties and performance of polymer materials, in particular in nanofiller reinforced composites. Experimental efforts have been made to determine the effective interphase thickness and its properties, for example, by nanoindentation and nanoscratch techniques. Yet, it is very difficult to quantify the interphase and its properties because of its nanoscale nature and the unclear boundary. In this regard, computer simulation, e.g., molecular dynamics, provides an effective tool to characterize such interphase and the properties. In this work, molecular dynamics simulations are applied to quantify the interphase thickness in clay-based polymer nanocomposites. Then, the mechanical properties of the so-called effective nanofiller (i.e., the physical size of nanofiller plus the thickness of interphase) will be determined by a series of simulations.

Molecular Basis of Glucose Transport Mechanism in Plants

2019 ◽  
Author(s):  
Balaji Selvam ◽  
Ya-Chi Yu ◽  
Liqing Chen ◽  
Diwakar Shukla
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Molecular Dynamics Simulations ◽  
Conformational Changes ◽  
Transport Mechanism ◽  
Conformational Dynamics ◽  
Site Directed Mutagenesis ◽  
Free Energy Barrier ◽  
Transport Cycle ◽  
Dynamics Simulations

<p>The SWEET family belongs to a class of transporters in plants that undergoes large conformational changes to facilitate transport of sugar molecules across the cell membrane. However, the structures of their functionally relevant conformational states in the transport cycle have not been reported. In this study, we have characterized the conformational dynamics and complete transport cycle of glucose in OsSWEET2b transporter using extensive molecular dynamics simulations. Using Markov state models, we estimated the free energy barrier associated with different states as well as 1 for the glucose the transport mechanism. SWEETs undergoes structural transition to outward-facing (OF), Occluded (OC) and inward-facing (IF) and strongly support alternate access transport mechanism. The glucose diffuses freely from outside to inside the cell without causing major conformational changes which means that the conformations of glucose unbound and bound snapshots are exactly same for OF, OC and IF states. We identified a network of hydrophobic core residues at the center of the transporter that restricts the glucose entry to the cytoplasmic side and act as an intracellular hydrophobic gate. The mechanistic predictions from molecular dynamics simulations are validated using site-directed mutagenesis experiments. Our simulation also revealed hourglass like intermediate states making the pore radius narrower at the center. This work provides new fundamental insights into how substrate-transporter interactions actively change the free energy landscape of the transport cycle to facilitate enhanced transport activity.</p>

Multicanonical Molecular Dynamics Simulation Study of the Liquid-Solid and Solid-Solid Transitions in Lennard-Jones Clusters

2011 ◽  
Author(s):  
Toshihiro Kaneko ◽  
Kenji Yasuoka ◽  
Ayori Mitsutake ◽  
Xiao Cheng Zeng
Keyword(s):  
Molecular Dynamics ◽  
Heat Capacity ◽  
Transition Temperature ◽  
Peak Position ◽  
Temperature Curve ◽  
Dynamics Simulation ◽  
Lennard Jones ◽  
Dynamics Simulations ◽  
First Time ◽  
Good Agreement

Multicanonical molecular dynamics simulations are applied, for the first time, to study the liquid-solid and solid-solid transitions in Lennard-Jones (LJ) clusters. The transition temperatures are estimated based on the peak position in the heat capacity versus temperature curve. For LJ31, LJ58 and LJ98, our results on the solid-solid transition temperature are in good agreement with previous ones. For LJ309, the predicted liquid-solid transition temperature is also in agreement with previous result.

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