A method for assessing the side chain orientations of histidine, asparagine, and glutamine as well as the protonation forms of histidine in protein structures.

摘要

In protein X-ray crystallography, it is sometimes impossible to distinguish N and O in amide side chains and N and C in His side chains, resulting in the 'flipped' conformations in these side chains. We have developed a simple, but effective, approach to assess the side chain orientations of His. Asn, and Gln as well as the protonation forms of His in protein structures. This method finds the most favorable side chain orientation and His form by calculating the van der Waals interaction and hydrogen bonding energies around each residue in question. This evaluation is repeated until consistent results are obtained. Our approach was applied to four proteins and in overall approximately 25% of His, Asn, and Gln were evaluated as 'flipped' and 63% of the imidazole rings were suggested to have a polar hydrogen atom only on N epsilon2. In the individual cases, it was found that our results were comparable to or even better than those obtained by a traditional method. The present approach is therefore quite useful to construct initial protein structures for the molecular modeling studies.