Why we need protein crystals.

Interestingly solving the structure of a protein molecule using X-ray diffraction requires the protein molecule to be in a crystalline lattice (Fig. 1 is a representation of a crystal lattice). The main reason for this is quite simple. The structural information acquired is significantly amplified from diffracting X-rays off of millions of identically arranged protein molecules in a crystalline lattice. In order for you to get a better grasp of this fact we’ll have to explore a few of the finer points of X-ray diffraction from crystals. So here we go, X-rays are photons that behave like waves (and particles but I don’t want to even think about quantum mechanics). When X-rays are “in phase” the wave peaks and valleys line up (Fig. 2 demonstrates how the top two waves are in phase and when added produce the bottom wave with higher peaks and valleys). This is important because in an X-ray diffraction experiment when diffracted X-rays line up “in phase” (Fig. 3 demonstrates two incoming X-rays “in phase” that bounce off two electron dense planes "in phase" resulting in diffraction) they augment one another leading to a diffracted wave that has larger peaks and valleys. This diffracted X-ray can now be measured due to the amplification of its peaks and valleys from the crystalline lattice. The diffracted X-rays contain information necessary to solve the structure of the protein molecule because the diffracted X-rays produce a diffraction pattern (see Fig. 4 depicts a standard diffraction pattern) that is intimately connected to the structure of the protein molecule within the crystal. The diffraction pattern and a protein molecule are somewhat analogous to the fingerprint and a finger as the structure of both the protein and finger produce a unique diffraction pattern or fingerprint, respectively. The features of the diffraction pattern are mathematically described by Bragg’s law (see Fig. 5 – the mathematical equation for Bragg’s law) which illustrates the geometric conditions within the crystal lattice necessary for X-ray waves to be “in phase” during the diffraction experiment. The diffraction pattern from a typical X-ray diffraction experiment is essentially a manifestation of Bragg’s law.
As I mentioned in my previous post, diffraction data provides the intensity information required to solve the protein's structure but it lacks the phase information also necessary to solve the protein structure. In my next post I will describe how the protein crystallographer gathers this phase information and solves what is known as “the phase problem.”