Section 20.2.5. Modifications in the force field for structure determination

Simulated-annealing protocols require modification of the parameters to maintain the correct geometry and local structural integrity of the molecule in order to allow heating to very high, non-physical temperatures for several thousand integration steps. Such modifications are acceptable in the case of structure determination since the primary goal is to define the optimum equilibrium structure in best agreement with the crystallographic or NMR data. Simulations intended to reproduce the fluctuations or dynamic properties of the system must employ carefully defined parameters without such modifications. These modifications include substantial increases in the force constants for bond lengths and angles, e.g., factors of two to ten are used in the parameters specified in the X-PLOR file parallhdg.pro. A number of improper torsional terms are added to maintain proper chirality.

The specific terms in are also modified for the purpose of structure determination. In this methodology, the goal is to converge efficiently to a model that satisfies the experimental data, rather than to obtain an accurate description of the conformational surface, such as estimating fluctuations and equilibrium distributions. Alterations in include the replacement of the computationally expensive by a quartic or harmonic repulsive term, which prevents steric conflict among atoms, but ignores dispersive attraction. The electrostatic term, , is frequently excluded altogether, since the 1/r dependence of the Coulombic potential allows charge interactions to dominate the interatomic forces far from the global minimum in a fashion that hinders movement toward the global minimum. Exclusion of this important physical property of biological systems is possible, because the crystallographic structure factors contain sufficient information to reflect adequately the imprint of electrostatics on the average structure.