Restraints/restrained

You can include geometric restraints—for interatomic distances, bond angles, and torsion angles—in any molecular dynamics calculation or geometry optim i/.ation. Here are some applications of restrain ts ... 

Note Restraints apply to distances, angles and dihedrals between bonded ornon bonded atoms. Yon can also restrain atoms to points in space. 

You need to specify two parameters the et uilibrium value ofthe internal coordinate and the force constant for the harmonic poten tial, T h e equilibrium restraint value deperi ds on the reason you choosea restraint. If, for example, you would like a particular bond length to remain constant during a simulation, then the equ ilibritirn restrain t value would probably be Lh e initial len gth of the bond. If you wan t to force an internal coordinate to a new value, the equilibrium internal coordinate is the new value. 

Note You can superimpose harmonic restraining forces to interatomic distances, angles, or dihedrals that you have set up as named selections. Yon can also restrain atoms to points in space. See Using Geometric Restraints" on page SI and "Restraints" on page 105. 

I lie default restraints are appropriate for molcciilar dyriam ics calculations where larger force constants would create undesirable h igh frequency motion s hut much larger force con slants may be desired for restrained geometry oplim i/ation. ... 

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. 

In the flexibihty method, a basic anchor is assigned and the entire system is worked in reference to this basic anchor. The pipe is left free to expand from the basic anchor and all the other anchors and restraints are considered as released. The forces and moments are then appHed to the release anchor and restrained points to force those points back to their installed locations. Therefore, finding those forces and moments is required. 

Finally, an alchemical free energy simulation is needed to obtain the free energy difference between any one substate of system A and any one substate of system B, e.g., Ai- In practice, one chooses two substates that resemble each other as much as possible. In the alchemical simulation, it is necessary to restrain appropriate parts of the system to remain in the chosen substate. Thus, for the present hybrid Asp/Asn molecule, the Asp side chain should be confined to the Asp substate I and the Asn side chain confined to its substate I. Flat-bottomed dihedral restraints can achieve this very conveniently [38], in such a way that the most populated configurations (near the energy minimum) are hardly perturbed by the restraints. Note that if the substates AI and BI differ substantially, the transfomnation will be difficult to perform with a single-topology approach. 

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. 

Hemi-eder, n. hemihedron, hemihedral form or cr> stal. -edrie,/, hemihedrism. hemiedrisch, a. hemihedral. Hemimeilit(h)saure,/. hemimellitic acid, hemitrop, a. (Cryat.) hemitrope, twinned, Hemme, /. hindrance, restraint, impediment, obstruction arrest brake, hemmen, v.t. stop, check, arrest, inhibit, restrain retard brake clog,... 

If all nuclei are assigned and the spectral parameters for the conformational analysis are extracted, a conformation is calculated - usually by distance geometry (DG) or restrained molecular dynamics calculations (rMD). A test for the quality of the conformation, obtained using the experimental restraints, is its stability in a free MD run, i.e. an MD without experimental restraints. In this case, explicit solvents have to be used in the MD calculation. An indication of more than one conformation in fast equilibrium can be found if only parts of the final structure are in agreement with experimental data [3]. Relaxation data and heteronuclear NOEs can also be used to elucidate internal dynamics, but this is beyond the scope of this article. 

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