Hi Deepak,

With regards observed pKa shifts, Prof. Ondrechen from Northeastern University has had a long interest in this field.

Under the computational tools that she has developed a program called THEMATICS that allows you to predict the pka of titratable amino acids and she has been able to predict shifts. Though the server seems to be down at this point, here is the reference: Y. Wei, J. Ko, L.F. Murga, and M.J. Ondrechen, BMC Bioinformatics 8:119, (2007)

From the commercial side, Dr. Spassov from Accelrys has also been working on tools that predict protein ionization. In his work, he has also been able to predict significant pka shifts for functionally relevant residues.

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2578799/

Cheers,

Francisco

From: CCP4 bulletin board [mailto:[log in to unmask]] On Behalf Of Deepak Oswal
Sent: Tuesday, February 07, 2012 3:48 AM
To: [log in to unmask]
Subject: [ccp4bb] On pKa of Aspartic acid

Dear colleagues,

We have solved the crystal structure of a human enzyme. The pKa of a catalytically critical aspartic acid has increased to 6.44. It is hydrogen bonded (2.8 Angstroms) to a water molecule that is supposed to donate a proton during the catalysis. Can anybody help me a) interpret the significance of this increase in pKa of the aspartic acid from 3.8 to 6.44 in context with the catalysis? Is this advantageous or detrimental? b) How is pKa related to an amino acids’ ability to force a water molecule to donate a proton? c) At pH 7.4, the aspartic acid would be de-protonated irrespective of whether the pKa is 3.8 or 6.44; isn’t that true? d) Have similar increase in pKa values observed for aspartic acids before? I would be grateful if anybody could explain or comment on the above queries.

Deepak Oswal