Molekülersatz

Molekülersatz, a German term translating to "molecular replacement," is a technique used in structural biology, particularly in X-ray crystallography, to determine the three-dimensional structure of a crystalized molecule. It is an alternative method to de novo phasing or direct methods when the phase information cannot be easily obtained. The core principle of molecular replacement is to use the known structure of a similar molecule, referred to as the "search model," to solve the phase problem of the unknown structure.

The process begins with obtaining diffraction data from the crystal of the molecule of interest. Simultaneously, a homologous structure with a solved atomic resolution must be available. This search model is then systematically rotated and translated within the unit cell of the unknown crystal's diffraction pattern. The goal is to find the orientation and position of the search model that best matches the observed diffraction intensities. Mathematical algorithms are employed to perform this search, often involving minimizing the differences between calculated and observed structure factor amplitudes.

Once a plausible solution is found, it provides initial phase estimates for the unknown structure. These phases are then refined using iterative cycles of Fourier transformation and model building. Molecular replacement is particularly effective when the unknown molecule shares significant sequence homology with a molecule whose structure is already known. It significantly accelerates the structure determination process, especially for larger and more complex macromolecules.