Direct methods preliminary refinement

A preliminary knowledge of the crystal structure is important prior to a detailed charge density analysis. Direct methods are commonly used to solve structures in the spherical atom approximation. The most popular code is the Shelx from Sheldrick [26] which provides excellent graphical tools for visualization. The refinement of the atom positional parameters and anisotropic temperature factors are carried out by applying the full-matrix least-squares method on a data corrected if found necessary, for absorption and diffuse scattering. Hydrogen atoms are either fixed at idealized positions or located using the difference Fourier technique. 

Recently, Lindorff-Larsen el al.uo included the order parameter (S 2) in the target function, and refined an ubiquitin X-ray structure by restrained molecular dynamics (Section 6.4) to obtain an NMR structure ensemble (Section 6.5) from the trajectories. They simulated the values of RDCs (Section 9.1) and side chain scalar coupling from the calculated ensemble to confirm that the method can determine the protein three-dimensional structure and dynamic structure simultaneously. The simulated values were in good agreement with the corresponding measurement data. The simulation accuracy was improved from the preliminary calculated structure without the order parameters. The approach is typically important, because they tried to link the ensemble with a dynamic structure directly. 

Various physical considerations can be used for preliminary estimation of mathematic expressions and parameter values (rather simplified considerations were used in O Eqs. 9.2-9.S). It is important to emphasize that neither dependences nor values of parameters can be derived (directly calculated) from imiversal principles or measured by any experimental method. The stretch and bend constants (of O Eqs. 9.2 and O 9.3) can be evaluated using infra-red spectra equilibrium bond lengths and valence angles can be estimated from X-ray data for simple molecules. The Aij coefficients of the attraction part of van der Waals interactions can be evaluated (and really were calculated and used without refinement in the first MM works) via approximate formulae for dispersion interactions however, their exact values for the certain dass of the systems should be adjusted by comparison with experimental data... 

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