Date Published: March 30, 2011
Publisher: Public Library of Science
Author(s): Jun Liu, Da-Chuan Yin, Yun-Zhu Guo, Xi-Kai Wang, Si-Xiao Xie, Qin-Qin Lu, Yong-Ming Liu, Vladimir Uversky. http://doi.org/10.1371/journal.pone.0017950
Abstract: Protein crystals usually grow at a preferable temperature which is however not known for a new protein. This paper reports a new approach for determination of favorable crystallization temperature, which can be adopted to facilitate the crystallization screening process. By taking advantage of the correlation between the temperature dependence of the second virial coefficient (B22) and the solubility of protein, we measured the temperature dependence of B22 to predict the temperature dependence of the solubility. Using information about solubility versus temperature, a preferred crystallization temperature can be proposed. If B22 is a positive function of the temperature, a lower crystallization temperature is recommended; if B22 shows opposite behavior with respect to the temperature, a higher crystallization temperature is preferred. Otherwise, any temperature in the tested range can be used.
Partial Text: After the successful accomplishments of the Human Genome Project (HGP), more and more scientists have concentrated considerable interest on solving molecular-based diseases, which can be treated by structure-based rational drug design. Obtaining the 3-dimensional structure of the target biomacromolecules, which are often proteins, is the key to success in achieving this goal. Due to the potentially important applications of the structural information in human health, researchers have been making broad efforts to investigate the structures and functions of many proteins. It is well known that X-ray crystallography is the most widely used method to determine the 3-dimensional structure of proteins. More than 85% of the structures in the PDB (www.pdb.org) were determined by this method, which requires high quality protein crystals as diffraction targets. However, due to the complexity in crystal nucleation and growth, obtaining satisfactory protein crystals is often the rate-limiting step for structure determination. For example, over 60% of the targets for most commercial therapeutic drugs are membrane proteins , , which are usually hard to crystallize. Therefore, growing high quality protein crystals is an important task for structural biologists , .