Improving Conformer Populations with NOE-refinement… there are right ways and wrong ways…..

Congrats to Jess and Casper on the publication of their PCCP paper “Improved NOE fitting for flexible molecules based on molecular mechanics data – a case study with S-adenosylmethionine”. In a nutshell it highlights the improvements that are possible by appropriate treatment of NOE data when used to refine the conformer populations obtained from molecular dynamics. This is a key problem in modern computation… MD is great at getting you near the right answer, but not great at getting you THE right answer, so using experimental data to refine it is crucial – but we think this is often done poorly in literature studies (and hopefully in this article we do it well!).

 

Congratulations Jess!

Jess has just submitted the final version of her PhD thesis on “Optimisation and Application of Interproton Distances Measured by NOE Spectroscopy”  and is awaiting the official “You can call yourself Dr”.

Well done Dr Bame!

Stereochemistry in complex, flexible molecules

Well done Siying! Her work has just been published, in Nature, on the re-evaluation of the stereochemistry of Baulamycins A & B- working out the correct isomer from 128 possible diastereomers from a combination of NMR+computation (which eliminated 120 diastereomers) and synthesis (which narrowed it down to the right structure). Craig was hoping it would be his 100th paper (it was his 99th), but you can’t have everything……

More Sensitive, High Resolution and Faster – all at the same time?!?!

Iyke’s latest paper outlines EXACT-PSYCHE – Broadband homodecoupled 1H NMR spectra, collected up to 4-times faster than the standard experiment (with some clever IST-based processing from our Krzysztof and Alexandra (University of Warsaw) and Carlos (MestreLab Research).

It’s a nice piece of work to round off a very successful PhD research program – well done Iyke!

 

Literally curing cancer….

[A wandering thought from Craig….] I always wanted to be either a rocket scientist or cure cancer….. I made a good start, when the compound I worked on during my PhD (tetranitromethane) was indeed studied as a rocket fuel additive. Now we’ve been involved (if only peripherally) in working on a cure for a cancer –  some beautiful work from Will Singleton [92]  (we did NMR DOSY and concentration measurements on the system), highlighted by the Brain Tumour Charity https://www.thebraintumourcharity.org/media-centre/news/research-news/water-insoluble-drug-high-grade/.

What exactly is a perverted tendril?

Well, if you want to know I suggest you have a look at Jonathan Clayden’s latest report in Chemical Science. It’s a beautiful exposition of chemical synthesis, analysis and computation, combined to understand the structure and dynamics of ‘faults’ in helixes formed by conformationally constrained polypeptides.

First Papers for Claire, Alex and Alice!

Claire’s first paper from her PhD research, shared with Alex and Alice from their undergraduate projects, has come out in The Analyst (http://pubs.rsc.org/en/content/articlepdf/2017/an/c6an02298g) today. A beautiful exposition of what NMR methods allow us to most efficiently, most easily and most accurately measure the 2- and 3-bond 13C-1H coupling constants (unfortunately no method does all three optimally, but read it to find out what might work best for you!).

Dr Ndukwe

Iyke passed his PhD viva on December 9th – having been grilled by Dr James Keeler and Professor Matt Crump. Congratulations Dr Ndukwe!

Fast, Safe and EXACT – ASAPHSQC acquisition.

Iyke’s  EXACT method for burst-sampled acquisition (see 14th July post below) in the direct dimension of NMR experiments has been extended in his latest paper to the reduction in duty-cycle of the demanding ASAP-HSQC experiment. The resulting EXACT ASAP-HSQC experiment can be acquired in as little as 6 seconds, allowing him to monitor reaction kinetics which occur on the second-minute timescale.

Whatever will he think of next? Well, who knows… but presumably it will happen ASAP. And be rather EXACT!

Craig, MestreLab Research and qNOE

Craig has just presented a webinar for MestreLab Research SL on quantitative NOE analysis for small molecules. It gives an outline of how we (currently!) analyse NOE data to extract accurate interproton distances, looks at some of the problems which can arise, how to circumvent (some of) them, and finally presents a couple of our recent case studies.