Constraint potential

Various ligands bind to their protein sites in a diffusive motion. Similarly, the distance between different ends of a folded macromolecule changes in a way which can be described as a diffusive motion in the presence of a constraint potential (that keeps the parts of the molecule near their folded configurations). Brownian-type diffusive motion in the absence of a restrictive potential is characterized by a diffusion constant (Ref. 6)... 

PPII helix-forming propensities have been measured by Kelly et al. (2001) and A. L. Rucker, M. N. Campbell, and T. P. Creamer (unpublished results). In the simulations the peptide backbone was constrained to be in the PPII conformation, defined as (0,VO = ( — 75 25°, +145 25°), using constraint potentials described previously (Yun and Hermans, 1991 Creamer and Rose, 1994). The AMBER/ OPLS potential (Jorgensen and Tirado-Rives, 1988 Jorgensen and Severance, 1990) was employed at a temperature of 298° K, with solvent treated as a dielectric continuum of s = 78. After an initial equilibration period of 1 x 104 cycles, simulations were run for 2 x 106 cycles. Each cycle consisted of a number of attempted rotations about dihedrals equal to the total number of rotatable bonds in the peptide. Conformations were saved for analysis every 100 cycles. Solvent-accessible surface areas were calculated using the method of Richmond (1984) and a probe of 1.40 A radius. 

The planning team will select and state the decision error limits based on such considerations as regulatory guidance natural matrix variability practical constraints (cost and schedule) physical constraints potential impacts on human health and the... 

As described in the Introduction, it is usually possible to consider the modeling of experimental data separately from the scheme actually used to move atoms about. Ideally, the different models should be able to be used in the different minimization or dynamics schemes. Thus, the subsequent sections describe the kind of data offered by NMR and the kinds of penalty functions or pseudo-energy terms that can be used to represent them. For convenience, we use nomenclature common to force field-based approaches where one refers to a distance constraint potential Vdc r) as a function of intemudear distance. 

Constraints Potential Gaps Potential Relevance to Results Justification for Methodology... 

We use the constraint potential described in Eqs. 29.2 and 29.3 for the calculation of AG(z) by thermodynamic integration. An MD simulation without a constraint potential has shown that the equilibrated position of the peptide agrees with the minimum of AG(z). 

In constrained simulations near the transition state, it is difficult to sample from the delta function constraint (3.41), especially if a Monte Carlo sampling is used. It is therefore convenient to approximate the constrained weight function (3.41) by using the Gaussian approximation of the delta function in Eq. (3.15). This Gaussian constraint corresponds to a harmonic constraint potential Vconstr,y(r) [30,32] ... 

Besides a prefactor, this amounts to adding an effective constraint potential... 

Figure 2 Distance constraint potentials according to equation (5). For the thick curve the exponents were chosen as m — 12 and = 6, for the thin curve as m = n = 2 in both cases W = 1...

Figure 3 Torsion angle constraint potentials according to equation (6) with W = 1, = 2. The constraint represented by the thick line was designed to allow a range from 0° to 60°, The use of two constraints allowing two nonoverlapping angle ranges is illustrated by the thin line...

Jones, W.P., Rigopoulos, S. Reduction of comprehensive chemistry via constraint potentials. Proc. Combust. Inst. 30, 1325-1331 (2005b)... 

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