Restraint potentials

A) it is reasonable to assume that neither a restraint potential nor a real vacuum boundary will have large impact on the free energy calculations. 

D. Bassolino-Klimas, R. Tejero, S. R. Krystek, W. J. Metzler, G. T. Montelione, R. E. Bruccoleri. Simulated annealing with restrained molecular dynamics using a flexible restraint potential theory and evaluation with simulated NMR constraints. Protein Sci. 1996, 5, 593-603. 

It can be shown that the potential of mean force W(x) can be calculated from the probability distribution p (x), obtained from a simulation using a restraint potential U(x), by... 

In some systems, it may be possible to limit the sampled region of phase space by using restraint potentials, so that the overall conformation of a molecule remains unchanged. When different force constants for these restraint potentials are used, the free energy difference can be extrapolated to a system without restraint potentials. 

NMR spectroscopy is a well-suited technique to study the membrane interactions of antimicrobial peptides by taking advantage of the orientational dependence of nuclear spin interactions. This paper discusses several solid-state NMR experiments to extend information on the peptide structure and dynamics as well as on the effect of antimicrobial peptides on model membranes. More specifically, studies of peptide dynamics by and N CP/MAS and static experiments were reported. A set of orientational restraint potentials for solid-state NMR observables in-eluding N chemical shift and N- H dipolar coupling was developed. The N-H X (X = N,0,S) intramolecular hydrogen bond in the series of 2(2 -heteroaryl)pyrroles and their trifluoroacetyl derivatives was examined by the H, N spectroscopy and density functional theory (DFT)... 

A set of orientational restraint potentials has been developed for solid-state NMR observables including N chemical shift and N- H dipolar coupling. Torsion angle molecular dynamics (MD) simulations with available experimental N chemical shift and N- H dipolar coupling as target values have been performed to determine orientational information of four membrane proteins and to model the structures of some of these systems in oligomer states. The results suggest that incorporation of the orientational restraint potentials into MD simulations provides an efficient... 

The problems that occur when one tries to estimate affinity in terms of component terms do not arise when perturbation methods are used with simulations in order to compute potentials of mean force or free energies for molecular transformations simulations use a simple physical force field and thereby implicitly include all component terms discussed earlier. We have used the molecular transformation approach to compute binding affinities from these first principles [14]. The basic approach had been introduced in early work, in which we studied the affinity of xenon for myoglobin [11]. The procedure was to gradually decrease the interactions between xenon atom and protein, and compute the free energy change by standard perturbation methods, cf. (10). An (issential component is to impose a restraint on the... 

In our implementation of SMD, modified versions of VMD and Sigma communicate with each other using a customized, lightweight protocol. Sigma sends atomic positions resulting from each molecular dynamics time step to VMD for display. When the user specifies restraints on parts of the displayed model, VMD sends them to Sigma, where they are converted into potential-well restraints added to the force field [21]. 

Fig. 9.24 A restraining potential that does not penalise struetures in which the distance lies between the leaver and upper distances di and and uses harmonie functions outside this range (left). The harmonic potentials may also he replaeed by linear restraints further from this region (right).

In a related way, ensemble molecular dynamics derives a pharmacophore using restrained molecular dynamics for a collection of molecules. A force field model is set up so that none of the atoms in each molecule sees the atoms in ainy other molecule. This enables the molecules to be overlaid in space. A restraint term is included in the potential, which forces the appropriate atoms or functional groups to be overlaid in space. 

Restraints add potential terms to a force field calculation, favoring the value that you specify in a restraint. The larger the value of the h arm on ic force con stan t, th e m ore tigh tly th e calculation restrain s the value. 

You need to specify two parameters the equilibrium value of the internal coordinate and the force constant for the harmonic potential. The equilibrium restraint value depends on the reason you choose a restraint. If, for example, you would like a particular bond length to remain constant during a simulation, then the equilibrium restraint value would probably be the initial length of the bond. If you want to force an internal coordinate to anew value, the equilibrium internal coordinate is the new value. 

The viscosity therefore replaces the restraint on diffusion arising from the interaction of atoms expressed by tire Morse potential in Swalin s treatment. 

In many cases, it is also helpful to have the path repel itself so that the transition pathway is self-avoiding. An acmal dynamic trajectory may oscillate about a minimum energy configuration prior to an activated transition. In the computed restrained, selfavoiding path, there will be no clusters of intermediates isolated in potential energy minima and no loops or redundant segments. The self-avoidance restraint reduces the wasted effort in the search for a characteristic reaction pathway. The constraints and restraints are essential components of the computational protocol. 

---