Distance constraint potential

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. 

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...

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)... 

The role of the potential energy is taken by the Dyana target function [8, 28] that is defined such that it is zero if and only if all experimental distance constraints and torsion angle constraints are fulfilled and all nonbonded atom pairs satisfy a check for the absence of steric overlap. A conformation that satisfies the constraints more closely than another one will lead to a lower target function value. The exact definition of the Dyana target function is ... 

Excited state potential and lifetime Markwick et al. [56] have studied possible tautomerisation events involving (multiple) proton transfer using the unbiased, collective dynamic distance constraint method. While in the ground... 

Fig. 9. Proximity relationships for residues in Cl relative to 316 in H8. Example of R1 distance mapping in rhodopsin. For each distance measurement, only two R1 side chains were in the protein, one fixed at the reference site 316, and the other at a site in the sequence 55-75. The R1 side chains were modeled based on crystal structure data with energy minimization subject to the experimentally determined distance constraint (shown). In each case, the measured distances in solution were in good agreement with those expected from the rhodopsin crystal structure. Substituted cysteine residues 65 and 68 most rapidly formed disulfide cross-links with the reference cysteine at 316 in H8. This is indicated by the dark bars connecting the potential disulfide partners.

The calculation for neocarzinostatin took about a month with 20 of 1.6 GHz Pentium 4 CPUs scheduled by SUN GRID engine. The computation time can be easily reduced by advanced CPUs and an increased number of GRID computing nodes. In the near future, the computation time for this size of calculations will be days or hours, and can become a routine process with full automation. If the calculation becomes a routine, there will be no need to care about differences in calculation qualities of the PDB coordinates (Section 2). By distance constraint files, the structures can be easily reproduced with equal calculation qualities. For this purpose, the deposition of the constraints file in the PDB is very important. The constraints file and order parameters (if available in the Biological Magnetic Resonance Data Bank) will be able to describe a unique NMR structural potentiality with dynamics as discussed in Section 10. 

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