Difference between revisions of "Team:Aalto-Helsinki/Model Setup"

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<div class="container">
 
<div class="container">
 
<div class="introtext">
 
<div class="introtext">
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<h3 style="color: #339999">Computational methods and simulation set-up</h3>
 +
 
<p id="paragraph">
 
<p id="paragraph">
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Lorem Ipsum is simply dummy text of the printing and typesetting industry. Lorem Ipsum has been the industry's standard dummy text ever since the 1500s, when an unknown printer took a galley of type and scrambled it to make a type specimen book <a href="#refl1" name="ref1">[1]</a>. It has survived not only five centuries, but also the leap into electronic typesetting, remaining essentially unchanged. It was popularised in the 1960s with the release of Letraset sheets containing Lorem Ipsum passages, and more recently with desktop publishing software like Aldus PageMaker including versions of Lorem Ipsum.
+
Molecular modeling methods ultimately aim for direct comparison with experimental measurements. As
 +
such, a good model of molecular interaction is essential. Quantum chemistry based Ab initio molecular
 +
dynamics methods aim to reduce the amount of �tting and guesswork required for accurate modeling
 +
of molecular interactions. However, such approaches are generally limited to small systems and short
 +
timescales due to the added computational demand[15]. In classical molecular dynamics, molecules are
 +
described using stick-and-ball models: spherical atoms are connected by springs that represent bonds. As
 +
such, internal molecular forces can be described by simple mathematical models. For example, Hooke's
 +
law can be used to describe bonded interactions, while non-bonded interactions can be described by
 +
Lennard-Jones potential.[13, 18]
 
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Contrary to popular belief, Lorem Ipsum is not simply random text <a href="#refl2" name="ref2">[2]</a>. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of "de Finibus Bonorum et Malorum" (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, "Lorem ipsum dolor sit amet..", comes from a line in section 1.10.32.
+
Molecular dynamics is based on numerical, step-by-step, evaluation of Newton's equations of motion.
 +
Due to the many-body nature of the problem, Newton's equations of motion are discretized and solved
 +
numerically. MD trajectories, that describe the time evolution of the system, consist of both position
 +
and velocity vectors of the particles in the system. The position and velocity vectors are reevaluated
 +
according to �nite time interval by using numerical integrators. The position vectors de�ne the geometric
 +
con�guration of the system while the velocity vectors de�ne the kinetic energy and temperature of the
 +
system.[13, 18, 15]
 
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<div class="basictext">
 
<div class="basictext">
 
<p id="paragraph">
 
<p id="paragraph">
−
Contrary to popular belief, Lorem Ipsum is not simply random text. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of "de Finibus Bonorum et Malorum" (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, "Lorem ipsum dolor sit amet..", comes from a line in section 1.10.32.
+
We investigated the behavior of DCD-1L in aqueous solvents at varying salt concentrations and tem-
 +
peratures using molecular dynamics. the simulations make use of the GROMOS force�eld parameter set
 +
53a6[17]. GROMOS53A6 is considered a united-tom force�eld, which maps a carbon and its associated
 +
apolar hydrogens as one interaction center. The parametrization of the force�eld is based on accurate
 +
reproduction of free enthalpies of hydration and apolar solvation of a wide range of compounds. The
 +
relative free enthalpy of solvation between apolar and polar environments is an important property in
 +
many biological phenomena, including protein folding and membrane formation.
 
</p>
 
</p>
 +
 +
<h4>System set-up</h4>
 +
 
<p id="paragraph">
 
<p id="paragraph">
−
Contrary to popular belief, Lorem Ipsum is not simply random text. It has roots in a piece of classical Latin literature from 45 BC, making it over 2000 years old. Richard McClintock, a Latin professor at Hampden-Sydney College in Virginia, looked up one of the more obscure Latin words, consectetur, from a Lorem Ipsum passage, and going through the cites of the word in classical literature, discovered the undoubtable source. Lorem Ipsum comes from sections 1.10.32 and 1.10.33 of "de Finibus Bonorum et Malorum" (The Extremes of Good and Evil) by Cicero, written in 45 BC. This book is a treatise on the theory of ethics, very popular during the Renaissance. The first line of Lorem Ipsum, "Lorem ipsum dolor sit amet..", comes from a line in section 1.10.32.
+
We probed the behavior of a single DCD-1L solvated in water with added 2 Na+ counter-ions to neutralize
 +
the net negative charge of the peptide, as well as added salt (NaCl), with the salt concentrations varying
 +
from 20 mM to 500 mM. Additionally we probed the temperature dependency of DCD-1L structure
 +
by simulating a single peptide in water with 2 Na+ counter-ions at temperatures of 290 K, 300 K,
 +
310 K and 320 K. All the simulation trajectories were calculated using the Gromacs v.4.6.7 simulation
 +
package[19, 20].
 
</p>
 
</p>
 
<p id="paragraph">
 
<p id="paragraph">
−
It is a long established fact that a reader will be distracted by the readable content of a page when looking at its layout. The point of using Lorem Ipsum is that it has a more-or-less normal distribution of letters, as opposed to using 'Content here, content here', making it look like readable English. Many desktop publishing packages and web page editors now use Lorem Ipsum as their default model text, and a search for 'lorem ipsum' will uncover many web sites still in their infancy. Various versions have evolved over the years, sometimes by accident, sometimes on purpose (injected humour and the like).
+
As starting structure for our simulations, chose the helical crystal structure of dermcidin derived
 +
by Song et al.[6] available in the RCSB protein Data Bank (entry 2YMK). Due to the presence of
 +
missing atoms in the original model by Song et al., we constructed a a homology model based on
 +
the DCD-1L sequence used in our laboratory constructs using the SWISS-MODEL automated protein
 +
structure homology-modeling server[21, 22, 23, 24]. The resulting structure was then mapped to the
 +
GROMOS53A6 force�eld using the Gromacs 4.6.7 tool pdb2gmx.
 +
</p>
 +
</div>
 +
 
 +
<p id="paragraph">
 +
In all simulations, the dimensions of the simulation box were cubic with a side length of 11.2 nm. The
 +
peptide was inserted and centered into the simulation box and solvated in water. For all simulations,
 +
the simple point-charge (SPC) water model was used. After solvation, two of the water molecules were
 +
replaced by 2 Na+ ions to act as counter-ions and e�ectively neutralize the charge on the simulated
 +
system. Additionally, for simulations involving added salt, an adequate number of water molecules were
 +
replaced by an equal number of Na+ and Cl􀀀 ions to mimic the desired salt concentration of either 20
 +
mM, 50 mM, 70 mM, 100 mM, 120 mM, 150 mM, 200 mM, 300 mM or 500 mM. Visualizations of the
 +
simulated system set-up con�gurations are presented in �gure X.
 +
</p>
 +
</div>
 +
 
 +
<p id="paragraph">
 +
Prior to the production run, each simulation system was energy minimized using the steepest descent
 +
algorithm. this energy minimization was followed by 0.5 ns NVT equilibration with a time step of
 +
2 fs. During NVT equilibration, the temperature was controlled by the stochastic velocity rescaling
 +
thermostat developed by Bussi et al. [25] with �T = 0:1 ps. The NVT equilibration was followed by
 +
NPT equilibration for 1 ns with a time step of 2 fs. During the NPT equilibration, the pressure of
 +
the system was set to 1.0 bar using the isotropic Parrinello-Rahman [26] pressure control with �p = 2:0
 +
ps. The temperature was controlled by the stochastic velocity rescaling thermostat by Bussi et al. [25]
 +
with �T = 0:1 ps. During both NVT and NPT equilibration runs, position restrains were applied to the
 +
protein structure.
 +
</p>
 +
</div>
 +
 
 +
<p id="paragraph">
 +
For the production run, the pressure of the system was set to 1:0 bar using the isotropic Parrinello-
 +
Rahman [26] pressure control with �p = 12 ps. The temperature was controlled by the stochastic
 +
velocity rescaling thermostat by Bussi et al. [25] with �T = 0:1 ps. A time-step of 20 fs was used. For
 +
all equilibration and production runs, electrostatic interactions were calculated using the Particle-Mesh
 +
Ewald method[27] and periodic boundary conditions were applied. The simulation time of the systems
 +
varied from 50 ns to 100 ns, depending on the system.
 +
</p>
 +
</div>
 +
 
 +
<p id="paragraph">
 +
Analysis of the simulation trajectories was carried out using Gromacs 4.6.7 built-in tools and visual-
 +
ization of trajectories was accomplished using VMD[28]. Assignment of secondary structure elements of
 +
the peptide was done using a Gromacs interface for DSSP[29, 30].
 
</p>
 
</p>
 
</div>
 
</div>

Revision as of 15:15, 28 October 2017

Aalto-Helsinki




Computational methods and simulation set-up

Molecular modeling methods ultimately aim for direct comparison with experimental measurements. As such, a good model of molecular interaction is essential. Quantum chemistry based Ab initio molecular dynamics methods aim to reduce the amount of �tting and guesswork required for accurate modeling of molecular interactions. However, such approaches are generally limited to small systems and short timescales due to the added computational demand[15]. In classical molecular dynamics, molecules are described using stick-and-ball models: spherical atoms are connected by springs that represent bonds. As such, internal molecular forces can be described by simple mathematical models. For example, Hooke's law can be used to describe bonded interactions, while non-bonded interactions can be described by Lennard-Jones potential.[13, 18]

Molecular dynamics is based on numerical, step-by-step, evaluation of Newton's equations of motion. Due to the many-body nature of the problem, Newton's equations of motion are discretized and solved numerically. MD trajectories, that describe the time evolution of the system, consist of both position and velocity vectors of the particles in the system. The position and velocity vectors are reevaluated according to �nite time interval by using numerical integrators. The position vectors de�ne the geometric con�guration of the system while the velocity vectors de�ne the kinetic energy and temperature of the system.[13, 18, 15]

A good sailor knows everything is always changing. But so does a Buddhist monk - so would monks be good sailors?
Good Sailor

We investigated the behavior of DCD-1L in aqueous solvents at varying salt concentrations and tem- peratures using molecular dynamics. the simulations make use of the GROMOS force�eld parameter set 53a6[17]. GROMOS53A6 is considered a united-tom force�eld, which maps a carbon and its associated apolar hydrogens as one interaction center. The parametrization of the force�eld is based on accurate reproduction of free enthalpies of hydration and apolar solvation of a wide range of compounds. The relative free enthalpy of solvation between apolar and polar environments is an important property in many biological phenomena, including protein folding and membrane formation.

System set-up

We probed the behavior of a single DCD-1L solvated in water with added 2 Na+ counter-ions to neutralize the net negative charge of the peptide, as well as added salt (NaCl), with the salt concentrations varying from 20 mM to 500 mM. Additionally we probed the temperature dependency of DCD-1L structure by simulating a single peptide in water with 2 Na+ counter-ions at temperatures of 290 K, 300 K, 310 K and 320 K. All the simulation trajectories were calculated using the Gromacs v.4.6.7 simulation package[19, 20].

As starting structure for our simulations, chose the helical crystal structure of dermcidin derived by Song et al.[6] available in the RCSB protein Data Bank (entry 2YMK). Due to the presence of missing atoms in the original model by Song et al., we constructed a a homology model based on the DCD-1L sequence used in our laboratory constructs using the SWISS-MODEL automated protein structure homology-modeling server[21, 22, 23, 24]. The resulting structure was then mapped to the GROMOS53A6 force�eld using the Gromacs 4.6.7 tool pdb2gmx.

In all simulations, the dimensions of the simulation box were cubic with a side length of 11.2 nm. The peptide was inserted and centered into the simulation box and solvated in water. For all simulations, the simple point-charge (SPC) water model was used. After solvation, two of the water molecules were replaced by 2 Na+ ions to act as counter-ions and e�ectively neutralize the charge on the simulated system. Additionally, for simulations involving added salt, an adequate number of water molecules were replaced by an equal number of Na+ and Cl􀀀 ions to mimic the desired salt concentration of either 20 mM, 50 mM, 70 mM, 100 mM, 120 mM, 150 mM, 200 mM, 300 mM or 500 mM. Visualizations of the simulated system set-up con�gurations are presented in �gure X.

Prior to the production run, each simulation system was energy minimized using the steepest descent algorithm. this energy minimization was followed by 0.5 ns NVT equilibration with a time step of 2 fs. During NVT equilibration, the temperature was controlled by the stochastic velocity rescaling thermostat developed by Bussi et al. [25] with �T = 0:1 ps. The NVT equilibration was followed by NPT equilibration for 1 ns with a time step of 2 fs. During the NPT equilibration, the pressure of the system was set to 1.0 bar using the isotropic Parrinello-Rahman [26] pressure control with �p = 2:0 ps. The temperature was controlled by the stochastic velocity rescaling thermostat by Bussi et al. [25] with �T = 0:1 ps. During both NVT and NPT equilibration runs, position restrains were applied to the protein structure.

For the production run, the pressure of the system was set to 1:0 bar using the isotropic Parrinello- Rahman [26] pressure control with �p = 12 ps. The temperature was controlled by the stochastic velocity rescaling thermostat by Bussi et al. [25] with �T = 0:1 ps. A time-step of 20 fs was used. For all equilibration and production runs, electrostatic interactions were calculated using the Particle-Mesh Ewald method[27] and periodic boundary conditions were applied. The simulation time of the systems varied from 50 ns to 100 ns, depending on the system.

Analysis of the simulation trajectories was carried out using Gromacs 4.6.7 built-in tools and visual- ization of trajectories was accomplished using VMD[28]. Assignment of secondary structure elements of the peptide was done using a Gromacs interface for DSSP[29, 30].

References

[1] Writers, YEAR. Name of article / book. Publication. Accessible at: [url here].
[2] Writers, YEAR. Name of article / book. Publication. Accessible at: [url here].
[3] Writers, YEAR. Name of article / book. Publication. Accessible at: [url here].
[4] Writers, YEAR. Name of article / book. Publication. Accessible at: [url here].
[5] Writers, YEAR. Name of article / book. Publication. Accessible at: [url here].