Introduction to Molecular Dynamics with GROMACS

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eally that it is a trade-off. PME is great, but also clearly slower than cut-offs. Longer cut-offs are alwaysbetter than short ones (but slower), and while switched interactions improve energy conservation they introduceartificially large forces. Using PME is the safe option, but if that’s not fast enough it is worth investigatingreaction-field or cut-off interactions. It is also a good idea to check and follow the recommendedsettings for the force field used.GROMACS uses a separate preprocessing program grompp to collect parameters, topology, andcoordinates into a single run input file (e.g. em.tpr) from which the simulation is then started (thismakes it easier to prepare a run on your workstation but run it on a separate supercomputer).As we just said, the command grompp prepares run input files. You will need to provide it withthe parameter file above, the topology, a set of coordinates, and give the run input file some name (otherwiseit will get the default topol.tpr name). The program to actually run the energy minimization ismdrun - this is the very heart of Gromacs. mdrun has a really smart shortcut flag called “-deffnm” to use a string you provide (e.g. “em”) as the default name for all options. If you want toget some status update during the run it is also smart to turn on the verbosity flag (guess the letter,or consult the documentation). The minimization should finish in a couple of minutes.Carefully equilibrating the water around the proteinTo avoid unnecessary distortion of the protein when the molecular dynamics simulation is started,we first perform an equilibration run where all heavy protein atoms are restrained to their starting positions(using the file posre.itp generated earlier) while the water is relaxing around the structure. Thisshould really be 50-100ps, but if that appears to be too slow you can make do with 10ps (5000 steps)here. Bonds will be constrained to enable 2 fs time steps. Other settings are identical to energy minimization,but for molecular dynamics we also control the temperature and pressure with the Berendsenweak coupling algorithm. This is mostly done by extending the parameter file used above:------pr.mdp------integrator = mdnsteps = 5000dt = 0.002nstlist = 10rlist = 1.0coulombtype = pmercoulomb = 1.0vdw-type = cut-offrvdw = 1.0tcoupl= Berendsentc-grps= protein non-proteintau-t = 0.1 0.1ref-t = 298 298Pcoupl= Berendsentau-p = 1.0compressibility = 5e-5 5e-5 5e-5 0 0 0ref-p = 1.0nstenergy = 100define= -DPOSRES
------------------For a small protein like Lysozyme it should be more than enough with 100 ps (50,000 steps) for thewater to fully equilibrate around it, but in a large membrane system the slow lipid motions can requireseveral nanoseconds of relaxation. The only way to know for certain is to watch the potential energy,and extend the equilibration until it has converged. To run this equilibration in GROMACS youshould once more use the programs grompp and mdrun, but (i) apply the new parameters, and (ii)start from the final coordinates of the energy minimization.Running the production simulationThe difference between equilibration and production run will be minimal: the position restraints andpressure coupling are turned off, we decide how often to write output coordinates to analyze (say, every100 steps), and start a significantly longer simulation. How long depends on what you are studying, andthat should be decided before starting any simulations! For decent sampling the simulation should be atleast 10 times longer than the phenomena you are studying, which unfortunately sometimes conflictswith reality and available computer resources. This will depend a lot on the performance of your computer,but one option is to first run a very short simulation so you have something to work with whilelearning the analysis tools, and in the meantime you can run a longer simulation in the background.Select the number of steps and output frequencies yourself, but for reasons you’ll see later it is recommendedto write coordinates at least every picosecond, i.e. 500 steps.------run.mdp------integrator = mdnsteps = < select yourself! >dt = 0.002nstlist = 10rlist = 1.0coulombtype = pmercoulomb = 1.0vdw-type = cut-offrvdw = 1.0tcoupl= Berendsentc-grps= protein non-proteintau-t = 0.1 0.1ref-t = 298 298nstxout = < select yourself! >nstvout = < select yourself! >nstxtcout = < select yourself! >nstenergy = < select yourself! >------------------Storing full precision coordinates/velocities (nstxout/nstvout) enables restart if runs crash (poweroutage, full disk, etc.). The analysis normally only uses the compressed coordinates (nstxtcout). Use thedocumentation to figure out the names of the corresponding files. Perform the production run with thecommands grompp and mdrun (remember the verbosity flag to see how the run is progressing).Analysis of the simulation
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