Stereochemically restrained refinement of macromolecular structures

Abstract

The chapter focuses on the practical application of stereochemically-restrained refinement to macromolecular crystals. Details of computational procedures and minimization algorithms are treated and need not be considered in routine applications. However, it is important to understand the nature of the function being minimized. Thorough structural refinement has become an integral part of macromolecular crystallography. The chapter describes some extensions of the current export versions of the programs that have been implemented or are envisioned. Atomic motion and conformational heterogeneity (or disorder) is major impediments to successful refinement. The use of Fourier transformations to compute structure factors and gradient vectors might greatly improve speed for large problems. There are numerous other improvements that can be envisioned including a method for modeling the fluid solvent, an appropriate treatment of the correlation between occupancy and thermal parameters of discrete solvent molecules, restraints for nonbonded contacts from crystal packing, inclusion of attractive potentials for nonbonded contacts, provision for refining partial structures, and proper estimation of standard deviations. Extensions such as these are expected to be important in realizing the goal of producing refined structural models that reproduce the diffraction patterns to within the accuracy of the measured data and which are compatible with prior stereochemical knowledge of macromolecules.