Hi Scott- We have seen that semiempirical (SE-QM) offers a reasonable accuracy vs. speed tradeoff that is quite applicable to refinement. DFT is probably more then required for refinements at "standard" resolutions since for most cases it probably won't give you much new information, but it will cost a lot more time and memory. But as with anything else, your experiences will probably depend upon the structures of interest. The PM6 Hamiltonian does a good job and we capture electrostatics, polarization, charge transfer, etc. in real-time at each phenix microcycle in order to model the chemistry within the active site. The 1AZM example I posted in the previous email illustrates how these influences are important. The ATP structure in the Newsletter is another good example: http://www.phenix-online.org/newsletter/ Let me know if you are interested in giving it a shot. We have waived the license fee for nonprofit, academic users: http://www.quantumbioinc.com/products/software_licensing Thanks! -Lance On Feb 10, 2014, at 8:45 AM, Scott Horowitz wrote:

Cool! I'll have to try that, I think. I'm curious about the choice of semi-empirical vs. DFT; is DFT still too slow to work in most cases?

Thanks, Scott

On Sun, Feb 9, 2014 at 11:46 AM, Lance Westerhoff wrote:

Hi Scott-

You are welcome to try out our plugin to phenix. As detailed in the recent Phenix newsletter, this tool uses a fast QM calculation within the active site and can capture the chemistry between the ligand, the Zn, and the surrounding residues. You do not need to define a prior restraints for the coordination sphere. For more information take a look at this link:

http://www.quantumbioinc.com/products/phenix_divcon

We have run several Zn systems. The following case study for example shows the importance of protonation and electrostatics in the active site and how these can influence refinement.

http://www.quantumbioinc.com/publications/show/CS-Xray_1AZM

Let me know if you have any questions!

-Lance ____________________ Lance M. Westerhoff, Ph.D. President and General Manager QuantumBio Inc.

WWW: http://www.quantumbioinc.com

On Feb 7, 2014, at 9:04 AM, Scott Horowitz wrote:

...

Hi, I'm trying to use phenix.ensemble_refinement, and my structure has several zinc atoms, both coordinated to amino acids and free imidazoles, and sometimes both. It looks as though it's not really understanding that the zincs really should stay more or less in their coordination spots, and are spending some time in kind of weird spots. I couldn't find anything documented that seems like it will help, unless there's some clever way to use the harmonic restraints for this that I haven't figured out.

And while I'm at it, I have another potentially related problem: the rfree of my final ensemble (0.27) is substantially higher than my input structure (0.24). And yes, I had been doing my refinement in phenix, with hydrogens added, and I optimized pTLS. If you're curious, this is a 1.9 A structure.

Any help and/or suggestions would be greatly appreciated!

Thanks, Scott

-- Scott Horowitz, Ph.D. Research Associate Howard Hughes Medical Institute

University of Michigan Department of Molecular, Cellular, and Developmental Biology Bardwell lab 830 N. University Ave, Room 4007 Ann Arbor, MI 48109 phone: 734-647-6683 fax: 734-615-4226 _______________________________________________ phenixbb mailing list [email protected] http://phenix-online.org/mailman/listinfo/phenixbb

_______________________________________________ phenixbb mailing list [email protected] http://phenix-online.org/mailman/listinfo/phenixbb

-- Scott Horowitz, Ph.D. Research Associate Howard Hughes Medical Institute

University of Michigan Department of Molecular, Cellular, and Developmental Biology Bardwell lab 830 N. University Ave, Room 4007 Ann Arbor, MI 48109 phone: 734-647-6683 fax: 734-615-4226 _______________________________________________ phenixbb mailing list [email protected] http://phenix-online.org/mailman/listinfo/phenixbb