Chemistry Reference
In-Depth Information
minimum, the diffusivity of the ligand and the curvature of the potential surface is
used. These calculations are rapid and have given good results [586].
In nonequilibrium free energy methods (NE), λ incremented n times in the
calculation (from o to 1). Here n is a constant for the calculation. Simulation
sampling are allowed and summed between increments [629].
The free energy difference between two states is in principle equal to the work
performed on the system. According to thermodynamics, this rule is for
isothermal, reversible processes linking two equilibrium states. However,
infinitely long processes are required for a switch (process linking two states) to
be truly reversible. There are thus switching approaches in free energy
simulations. In the switching method of Bennett's acceptance ratio (BAR) there
are switches in backward and forward directions to calculate differences of free
energies estimated from the lower bound of the average work. Other approaches
improve sampling of the switches
via
weights for size and position of increments.
In the method of bias sampling configuration, sampling is used for bias yielding
increments of λ [628].
In the non equibrilium harmonic oscillator approach (HO) sampling is made in A
and B systems with differing hamiltonians but the same number of oscillating
particles. Many of the properties, including free energy differences are calculated
analytically. This is useful for comparisons with correct answers [589].
There has been recent advances to construct biomolecular free energy landscape
from a MD simulation. In order to reduce the large number of MD trajectory
atomic coordinates, the method uses a systematic principal component analysis.
The system is reduced to few collective degrees of freedom. The protocol uses
internal coordinates (backbone dihedral angles in the dihedral angle PCA) to
avoid artifact mixing of internal and overall motion. The procedure also makes the
choice of an appropriate dimensionality of the energy landscape (containing all
slow large-amplitude motions of the molecule/neglecting coordinates describing
high-frequency fluctuations) [633].
Recent work reports the evaluation of the relative free energies of bio
organometallic compounds. The method explores the conformational space by
