Introduction to molecular replacement: a time perspective

Abstract

This article provides an introduction to the crystal phasing technique known as molecular replacement. The available software is reviewed, and the prospects for future developments are considered. Several examples are described in detail to illustrate potential problems. A brief account of past progress is included. The basic crystallographic equations underlying the procedures are given in an appendix.

Keywords: crystal phasing; crystallographic equations; crystallographic theory; history; molecular replacement; scoring functions; test cases.

Figure 1

(a) Sequence alignment and (b) overlap of PDB entries 2wce (blue), 1k9p (yellow) and 1k96 (brown), showing the domain movement between PDB entries 2wce and 1k96. (c) The difference electron density for Thr43, missing from the search model, after initial refinement to R and R _free factors of 46% and 49%, respectively. (d) Final electron-density map for Thr43 after Buccaneer rebuild: R = 22%

Figure 2

GroEL self rotation. Plots based on the data for PDB entry 5opx. The section at χ = 180° shows seven peaks relating the seven copies of GroEL to their symmetry pairings, and the section at χ = 51° (∼360/7) shows the directions of the two sevenfold axes.

Figure 3

Illustration of bootstrapping from a partial solution: progressive vitamin B₁₂ Fourier maps showing density for the corrin ring. (a) Co only. (b) Co + eight atoms. (c) Co + 17 atoms. (d) Complete.