I think this is pretty much the reason. Other than the fact that completely different methods are used to solve small molecule vs. macromolecular structures, there are a number of reasons that macromolecular structures aren't as easily/routinely solved.
A good starting point is to remember exactly what an R2 value tells us. It's an indication of the overall quality of the solution, and does not tell us anything about the quality of local (i.e. regional) refinements. In small molecule structures, the "local refinement" is basically the whole of the asymmetric unit. Providing you get that right, and select the correct space group, you've got the structure. It's pretty straight forward providing there's no twinning or disorder going on, and you know from your experiment what your molecule should look like. Macromolecules, on the other hand, are much more anisotropic and don't diffract as well. There's a lot more stuff going on in the diffraction pattern. You're depending on residues behaving like they do in other structures. If just one tiny little bit of the structure behaves unexpectedly, then you can model it wrong, and your solution is done for. (I'm not an expert in macromolecular crystallography, I trained as a small molecule crystallographer... so maybe my reasoning is far too superficial or simplistic) This is why, in my opinion, other statistical measures should be given their due attention in refinement of macromolecules. As for small molecules, an R2 value is a good general guide of the quality of your solution and refinements, but should not always be taken at face value. Of course, it all depends on what information you actually want from your experiment, too. Rachael Skyner PDRA (XChem) Diamond Light Source Ltd. Diamond House, Harwell Science & Innovation Campus, Didcot, Oxfordshire OX11 0DE Tel: +44(0)1235 56 7537 ________________________________________ From: CCP4 bulletin board [CCP4BB@JISCMAIL.AC.UK] on behalf of Tim Gruene [tim.gru...@psi.ch] Sent: 22 September 2017 22:42 To: ccp4bb Subject: Re: [ccp4bb] PAK=0 problem Hi James, small molecule structures usually model every or nearly every atom in the asymmetric unit - do you think that simple answer is too naive? Best, Tim On Friday, September 15, 2017 9:25:25 AM CEST James Holton wrote: > You know, I've been pondering that question for most of my adult life. > Why can't we push macromolecular R factors down to the level of > experimental error like our "small molecule" colleagues do routinely? I > have a few ideas, and others do too. In fact, there will be session on > this topic at the next ACA meeting. > [...] > -James Holton > MAD Scientist > > On 9/15/2017 4:32 AM, rohit kumar wrote: > > why R/Rfree not going down from 21/25? -- -- Paul Scherrer Institut Tim Gruene - persoenlich - OFLC/104 CH-5232 Villigen PSI phone: +41 (0)56 310 5297 GPG Key ID = A46BEE1A -- This e-mail and any attachments may contain confidential, copyright and or privileged material, and are for the use of the intended addressee only. If you are not the intended addressee or an authorised recipient of the addressee please notify us of receipt by returning the e-mail and do not use, copy, retain, distribute or disclose the information in or attached to the e-mail. Any opinions expressed within this e-mail are those of the individual and not necessarily of Diamond Light Source Ltd. Diamond Light Source Ltd. cannot guarantee that this e-mail or any attachments are free from viruses and we cannot accept liability for any damage which you may sustain as a result of software viruses which may be transmitted in or with the message. Diamond Light Source Limited (company no. 4375679). Registered in England and Wales with its registered office at Diamond House, Harwell Science and Innovation Campus, Didcot, Oxfordshire, OX11 0DE, United Kingdom
