Enhanced sampling of particular degrees of freedom in molecular systems based on adiabatic decoupling and temperature or force scaling

Abstract

A method to enhance sampling of a small subset of N(h) particular degrees of freedom of a system of N(h) + N(l) degrees of freedom is presented. It makes use of adiabatically decoupling these degrees of freedom by increasing their mass followed by either increasing their temperature or reducing their interaction or the force acting on them. The appropriate statistical-mechanical expressions for use of these methods in simulation studies are derived. As long as the subset of mass-increased degrees of freedom is small compared to the total number of degrees of freedom of the system, sampling of this subset of degrees of freedom can be much enhanced at the cost of a slight perturbation of the configurational distribution. This is illustrated for a test system of 1000 SPC, simple point charge, water molecules at 300 K and a density of 997 kg m(-3). Various fractions N(h)/(N(h) + N(l)) of water molecules were adiabatically decoupled to different degrees. The size of the diffusion coefficient of these decoupled water molecules was used as a measure for how much the sampling was enhanced and the average potential energy per water molecule was used as a measure of how much the configurational distribution of the system gets distorted. A variety of parameter values was investigated and it was found that for N(h)/(N(h) + N(l)) ≤ 0.1 the diffusion of the N(h) molecules could be enhanced by factors up to 35 depending on the method, the ratio N(h)/(N(h) + N(l)), the extent of adiabatic decoupling, and the temperature or force scaling factors, at the cost of a slight perturbation of the configurational distribution.

New functionalities in the GROMOS biomolecular simulation software

“…Here, we have denoted the masses of the N h h type particles collectively by m h and the ones of the N l remaining atoms collectively by m l . This decoupling is more easily achieved [10] if…”

“…where the ensemble average in the denominator is over the l type degrees of freedom [10] at T l . Applying force scaling, [10] the force acting on a h type degree of freedom is scaled by a factor s V ,…”

“…[10] A particular set of 3N h degrees of freedom can be adiabatically decoupled from the other 3N l degrees of freedom of the system by increasing the mass of the N h h type particles,…”

“…Applying force scaling, [10] the force acting on a h type degree of freedom is scaled by a factor s V ,…”

“…Here, we briefly describe some of the new functionalities that have been added since 2005: electronic polarizability, [6,7] an implicit surface area and internal volume solvation term [8] for the calculation of interatomic forces, functions required to use the GROMOS coarse-grained (CG) supramolecular force field, [9] a multiplicative switching function for nonbonded interactions, which replaces the one described in Ref. 5, adiabatic decoupling as a means to enhance the sampling of a not too large subset of degrees of freedom of a system, [10] and nonequilibrium molecular dynamics (MD) methodology to compute the dielectric permittivity and relaxation [11] or viscosity. The architecture and implementation of the GROMOS C++ code is described elsewhere, [12] as are features with regard to biomolecular structure refinement based on experimental NMR or X-ray data, [13] to the computation of relative free energies, [14] and the analysis of MD trajectories using GROMOS.…”