Induced Protonation State Changes Upon Binding
There was an interesting article published recently in the Biophysical Journal, (Volume 98, Issue 5, 872-880, 3 March 2010, doi:10.1016/j.bpj.2009.11.016), in which biophysicists recognise the importance of protonation state induced changes upon binding - and mention that one of its key practical applications is in structure-based drug design.
Dr. Alexey Onufriev from Virginia Tech and his team investigated three types (small molecule, protein and nucleic acid) of ligands and their ionization state changes upon protein-ligand binding. They concluded that in all tree cases substantial changes can be observed both in the ligand and also in the receptor ionization states upon binding.
This is a very important observation for virtual screening and docking, because this proves our belief that protonation states of the proteins and ligands can not and should not be prepared and / or fixed for virtual screening experiments. Therefore eHiTS’ method of assigning the protonation states on-the-fly is probably the best method to-date offered to solve this problem. For more info on eHiTS’ automated protonation state handling, please see our technical note with the same title on this page: http://www.simbiosys.com/ehits/ehits_technical_notes.html
posted by Aniko