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# Eléments de modélisation moléculaire

Monday 16 January 2006, by

Chaque logiciel de dynamique moléculaire fait appel à un ensemble de méthodes pour représenter un modèle moléculaire. Cet article présente les différents méthodes existantes ainsi qu’une brève explication de leur signification.

### Locally Enhance Sampling

LES was initially proposed by Elber and Karplus (jacs, (1990) 112:9161) to study carbon monoxide escaping through myoglobin. To improve sampling, many copies of a small part of the system (eg CO) are made, where the copies DO NOT interact each other, the interaction between the copies and the large part of the system (eg myoglobin) is scaled by the number of copies. In this way, the energy barrier that CO must overcome to scape is decreased, and the probability of observation of a scape is increased exponentially.

Many theoretical improvements in the method has been done by Ulitsky, Elber, Straub and Karplus (JCP (1993) 98:3380; JCP (1991) 94:6737; JPC (1994) 98:1034). Basically, they wanted to map the dynamics of each copy to the dynamics observed if there were not copies (ie one single CO) in order to observe correct time dependent properties.

*from M Sonoda, GROMACS user’s list*

### Cutoff, PME

Actually its not the cutoff that matters so strongly as

the distance to the face.

That is, PME energies and forces are independent of cutoff (the reciprocal parameters grid size and spline order along with ewald parameter beta need to adjust with the cutoff however). So, if it weren’t for the van der Waals terms which are also cutoff you could run pme with a cutoff of 4A and appropriate reciprocal parameters and do fine. On the other hand you could use a big cutoff of say 12A in your case and do fine. The one caveat here is that the cutoff must be less that 1/2 the smallest box dimension. This is due to amber’s use of the minimum distance criterion, which means that you can only calculate minimum image pairs; i.e. pairs that are within 1/2 the smallest dimension away (periodically wrapped if necessary).

So the real "law" is that you need plenty of water to screen undesired periodicity artifacts. That is you don’t want much interaction with your own periodic images. To understand this latter think of a continuum treatment where your protein is surrounded by a dielectric of 80, so (at least at a distance) electrostatic interactions go like E = 332*q1*q2 / (80*r12) or E 4*q1*q2/r12 where q1 and q2 are partial charges, r12 is distance between in angstroms and energy is in kcals.

So you would like plenty of distance (e.g. 20A) between protein and its periodic images. For a more quantitative view using Poisson-Boltzmann equation with periodic boundary conditions, see Hunenberger and mccammon Biophys Chem 78 pp69-88 April 1999

*From Tom Darden, AMBER mailing-list*

### Thermostat, bain thermostaté

**Q :** I hate to trouble you, but I was wondering if there was some way to get reasonable energy conservation for constant-energy (ntt=0) simulations without solvent when cutoffs are used in AMBER7. We’re trying to use GBSA and want to compute free energy differences in the canonical ensemble, and I’m a bit hesitant to use the Berendsen thermostat because many texts note it doesn’t sample from a proper canonical ensemble. We were therefore thinking of randomizing velocities every so often or using an Andersen-like thermostat. Unfortunately, energy conservation with reasonably finite cutoffs seems to be rather poor. Is there a force-switch function available in the nonbonded calculations? The switch eedmeth=3 seems to enable some sort of switch, but I’m afraid I couldn’t really tell what was going on from a cursory reading o the PME code in which nonbonded calculations now seem to be embedded.

**R :** There is no force switch currently implemented. The eedmeth=3 is related to PME, and is not active for GBSA simulations. Given the complexity of the long-range behavior of the GB potential, it is not clear how best to implement a smooth cutoff, which in any event, leads to the usual problems with cutoffs (even if it would conserve total energy).

Since the potential falls off rapidly with distance, in many cases a cutoff off of 15-20 Ang. will suffice; you can also play with nrespa (try up to 4), but we recognize the the GB method is not yet as efficient as we would like.

The Berendsen thermostat has a worse reputation than it really deserves, although for a small number of degrees of freedom (which you might have with implicit solvent) it can be less effective than other methods. You might want to look at:

%A T. Morishita

%T Fluctuation formulas in molecular-dynamics simulations with the weak coupling heat bath

%J J. Chem. Phys.

%V 113

%P 2976

%D 2000

Vrand is indeed roughly like an Andersen thermostat (depending on details of implementation. Note that, in its current form in Amber 7, the kinetic energy on the step where it is invoked is not good if SHAKE is being used.

This has no effect on the trajectory (and hence on any averages over coordinates or over potential energies), but it will influence what the system thinks the average temperature is, and the average and fluctuations in total energy.

..good luck....dac

*From D.A. Case, AMBER mailing-list*

### Traitement de l’eau

Le site http://www.lsbu.ac.uk/water/models.html explique les différentes représentations des molécules d’eau et compare leurs ressemblances/différences.

Sur la page principale http://www.lsbu.ac.uk/water/index.html, une présentation plus globale du solvant acqueux est réalisée.