All, I know Clemens Vonrhein raised a similar question about the HIS restraint target values & SUs in the standard library some years ago. The values currently in use appear to be the Engh & Huber (1991) ones for the doubly-protonated (+1 charge) imidazole side-chain, so I have 4 questions:
1) Shouldn't we be using the E&H (1999) values by now? 2) Is the doubly-protonated form the most appropriate, given that the pKa is supposed to be ~ 6 (I'm aware that the physiological extracellular pH of ~ 7.4 may not be relevant inside a protein)? 3) Do users have the option to use the parameters for the other forms (assuming of course they can work out for each case which form is present, and therein of course may lie the rub!)? E&H list values for 3 forms of HIS: 'HISE' with ND1 unprotonated, NE2 protonated; 'HISD' with ND1 protonated, NE2 unprotonated; and 'HISH' the doubly protonated form which appears to be the default. 4) Would a suitably weighted average of all 3 forms be more appropriate, with suitable inflation of the SUs, given that the form actually present is likely to be a mixture of tautomeric and/or resonance-charged/uncharged forms anyway? Cheers -- Ian ******************************************** Ian J. Tickle, DPhil. Director of X-ray Technology Astex Therapeutics Ltd 436 Cambridge Science Park Milton Road, Cambridge CB4 0QA, UK www.astex-therapeutics.com Disclaimer This communication is confidential and may contain privileged information intended solely for the named addressee(s). It may not be used or disclosed except for the purpose for which it has been sent. If you are not the intended recipient you must not review, use, disclose, copy, distribute or take any action in reliance upon it. If you have received this communication in error, please notify Astex Therapeutics Ltd by emailing [email protected] and destroy all copies of the message and any attached documents. Astex Therapeutics Ltd monitors, controls and protects all its messaging traffic in compliance with its corporate email policy. The Company accepts no liability or responsibility for any onward transmission or use of emails and attachments having left the Astex Therapeutics domain. Unless expressly stated, opinions in this message are those of the individual sender and not of Astex Therapeutics Ltd. The recipient should check this email and any attachments for the presence of computer viruses. Astex Therapeutics Ltd accepts no liability for damage caused by any virus transmitted by this email. E-mail is susceptible to data corruption, interception, unauthorized amendment, and tampering, Astex Therapeutics Ltd only send and receive e-mails on the basis that the Company is not liable for any such alteration or any consequences thereof. Astex Therapeutics Ltd., Registered in England at 436 Cambridge Science Park, Cambridge CB4 0QA under number 3751674
