Density modification

Since we will perform only an exploratory calculation with respect to the density modification, instead of highly sophisticated parameterization of the interaction such as the PARIS and BONN potential we will use a simple, separable Yamaguchi interaction. 

Often the initial phases from one of the above techniques (particularly MIR and MAD) are not sufficiently accurate to build in all the atoms and further improvement of the phases must be carried out. The standard approach for this is called density modification, or solvent-flattening. The idea is that if a unit cell contains a sufficient amount of solvent in it (usually around 50%, which is reasonable for most protein crystals), you will be able to use this information to improve the phases for the protein. The region of the unit cell that contains the solvent is set to an average value and new structure factors and phases are then calculated for... 

Cowtan, K. and Main, P. (1998). Miscellaneous algorithms for density modification. Acta Crystallogr. D 54, 487- 93. 

Cowtan, K. D. and Zhang, K. Y. (1999). Density modification for macromolecular phase improvement. Prog. Biophys. Mol. Biol. 72,245-270. 

TerwiUiger, T. C. (2001). Maximum-UkeUhood density modification using pattern recognition of structural motifs. Acta Crystallogr. D 57,1755-1762. 

TerwiUiger, T. C. (2003). SOLVE and RESOLVE automated structure solution and density modification. Method Enzymol. 374,22-37. 

One of the earliest ways of doing density modification is non-crystallographic symmetry averaging. Sometimes, different molecules in the asymmetric... 

In many ways, NCS averaging is the easiest density modification technique to intuitively understand, especially if considered in real space. In the process of NCS averaging, one simply takes all the different NCS related molecules in the as)un-metric imit, superimposes them, and then replaces their density with the average density. Because these... 

Some of the popular density modification programs implementing the real space restraints discussed above are Solomon (Abrahams, 1997), DM (Cowtan, 1999), RESOLVE (Terwilhger, 2003), Pirate (Cow-tan, http // www.ysbl.york.ac.uk/ cowtan/pirate/ pirate.html) and SHELXE (Sheldrick, 2002). 

Solomon. This was the first density modification program to use solvent flipping, where density in the solvent region is inverted or flipped to enhance... 

Availability http //solve.lanl.gov Pirate. A new statistically based density modification program that uses sparseness/denseness and order/disorder in a statistical framework to model a new protein structure from ones that have been previously determined. 

In this chapter we have presented the concept of density modification, where we take a priori information about the structure of the macromolecule we are studying to improve phase estimates. These... 

Cowtan, K. (1994). dm An automated procedure for phase improvement by density modification. Joint CCP4 and ESF-EACBM Newsletter on Protein Crystallography 31, 34-38. 

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