Monday, July 6, 2015

Genetically engineering short hydrogen bonds in a fluorescent protein

There is a very nice article in the new journal, ACS Central Science
Short Hydrogen Bonds and Proton Delocalization in Green Fluorescent Protein (GFP) 
Luke M. Oltrogge and Steven G. Boxer

This is an impressive piece of work spanning from molecular biology to chemistry to quantum physics.
There is also a commentary on the paper by Judith Klinman, placing it in the context of the controversial issue of low-barrier hydrogen bonds in enzymes.

An extensive study was made of mutants of the Green Fluorescent Protein with a short hydrogen bond between the chromophore and the amino acid Asp148. The donor-acceptor bond length estimated from X-ray structures was 2.4 +/- 0.2 Angstroms. This is in the range of low-barrier H-bonds.

What is particularly new here is that through ingenious molecular biology techniques [nonsense suppression] the acidity [pK_a = measure of tendency to give up protons] of the chromophore was systematically varied by 3.5 units through halogen substitutions.

This range covers the pK_a matching required for strongest H-bonds, as discussed in this earlier post. The experimental results were compared to calculations based on a one-dimensional proton transfer potential based on a diabatic state model I have advocated. It was very satisfying for me to see this simple model being used by experimentalists.

To me what is most striking about the paper is the UV absorption spectra below. It is very different from what one normally sees in GFP spectra.
There are generally two absorption bands, denoted A and B, associated with GFP. The A-state and B-state are identified with the neutral chromophore and anionic [i.e. deprotonated] chromophore, respectively. The corresponding spectra are similar to the black and grey curves shown above. The green spectrum above is for the Cl1Y substituted chromophore, which is close to pK_a matching, and is rather broad and intermediate between the A-state and B-state spectra. This is arguably because the proton is delocalised between the chromophore and neighbouring Asp amino acid.

The authors also substituted protons (H) with deuterium (D) to see the extent of quantum nuclear effects. These are normally very small in GFP. However, here they are noticeable.
The measured isotopic fractionation factors Phi (deduced from analysis of the UV absorption spectra) were in the range 0.54 - 0.9, taking a minimum value for pK_a matching. This observation and a value of Phi=0.54 for R=2.4 +/- 0.2 Angstroms are consistent with a recent theoretical analysis.

There is one point where I disagree with the theoretical analysis of the authors. I am confused that they average over the vibrational eigenstates to get an electronic absorption spectrum. This seems to me this goes against the Franck-Condon principle.  If one followed this same procedure for other molecules the UV spectra would all be much broader than they are, particularly in gas phase.
It is not clear to me how one should proceed in this situation where the proton is quite delocalised and the absorption spectra is significantly different for protonated and de-protonated chromophores. There may be significant Herzberg-Teller effects. One way forward to could be to combine the two-diabatic state H-bond model with a two-state resonance model for the chromophore, such as those advocated by Seth Olsen and I, and then do a full non-adiabatic treatment of the model.

I thank Luke Oltrogge and Seth Olsen for helpful discussions about this work.

Thursday, July 2, 2015

Do you want to be judged at the click of a mouse?

Then sign up for a Google Scholar account!

With one click people will not just see your publications but also how many times they have been cited. More problematic is that they will also see the values of different metrics such as your h-index and ten year h-index.

Recently, I encouraged someone on the job market to delete their account.

Unfortunately, there are people who will look at job and funding candidates and quickly dismiss them  if their metrics fall below certain threshold values. No consideration is given to scientific content, quality of publications, difficulty or popularity of the research field, career or personal history, .... People inevitably make unhealthy and unrealistic comparisons to "stars" and more senior people.
I have seen this happen.

I detest this and so I do not have my own account. Furthermore, I do not look at peoples pages just for the sake of it. I particularly think making comparisons with colleagues is very unhelpful.

So here are my reluctant and painful recommendations which some will disagree with.
Basically, unless you have "stellar" citations I would delete your page or not get one.
What are some rough numbers for h-index cutoffs? I would suggest.
Ph.D students should not have an account.
If you are a postdoc anything in single digits.
If you are junior faculty anything less than 20.
If you are senior faculty anything less than 30-40.

I stress I do not agree with this. I am just trying to protect you.
In an actual written application you can provide whatever citation information you choose. Furthermore, you have the opportunity to actually spell out your real scientific achievements and put your career in context.
Don't provide lazy evaluators with an easy option.

I welcome comments.

Wednesday, July 1, 2015

A nice write up in Physics World

Physics World [Magazine for the Institute of Physics (UK) = British equivalent of Physics Today] has a feature Web life that covers different web sites.

The June 2015 issue features this blog!
Besides the publicity, I was really happy because I felt the article nicely captured what I am on about. I was not interviewed and only heard about it from a Commenter, Peter Morgan.

One mild amusement was that I was classified as "a chemical physicist". I would certainly classify myself as a "condensed matter physicist" who sometimes tries to do chemical physics. So I took this as a compliment!

Tuesday, June 30, 2015

Cool experiments with dry ice

Yesterday my wife and I did our latest kids science demo gig, at a holidays kid club at our church. My son has encouraged us to come up with some new demonstrations since some of the kids have already seen some of the old favourites, such as Elephants toothpaste, coke and mentos rocket, and a few others here.

At first I was pretty excited when I saw this Youtube video of an LED powered by a lemon. Watch it and see what you think. I even got some LEDs to tried and do it. At the end of the post I tell the rest of the story.

We settled on a few demos with dry ice [solid carbon dioxide]. The unique feature is that at atmospheric pressure the solid does not melt [become liquid] but sublimates [becomes vapour]. This is because in the phase diagram the pressure of the triple point [5 atm] is above atmospheric pressure.

Here are some of the demonstrations. Many of them rely on the simple fact that the volume of one gram of vapour is of the order of five hundred times larger than the volume of one gram of solid. A good exercise for high school and college students [and you!] is to come up with a simple "back of the envelope" argument as to why this is so.

A. Put a few pellets of dry ice in a zip lock bag and seal it.
After a few minutes the pressure build up due to sublimation causes the bag to "pop". I quite like this because the pop is not so loud that it scares little children and the bag is usually not damaged and so you can keep doing this again and again. Each kid gets to have bag.

B. Dry ice in a balloon. Just add a few pellets to a balloon and tie it up. Wait a few minutes and it will expand, and perhaps pop.

C. Smash a gummy bear [snake in Australia]. Make as slurry of dry ice and car antifreeze. Add a gummy bear. Take it out and smash it with a hammer. Aside: a technical discussion is here.

D. The cauldron. Simply add dry ice to some water and watch it "boil". This should actually lead to a good discussion of the difference between "bubbling" and "boiling".

Here is one compilation including a massive soap bubble by the "Crazy Russian Hacker". I did not do all of these!

In the USA I believe you can buy dry ice at some grocery stores. In Australia, it is harder; we had to go to a BOC Gas and Gear store in Brisbane and buy 1 kg of pellets for $10. They last about half a day before they completely sublimate. Pellets are easier to work with, but they don't last as long.

Postscript. The Youtube video of the LED lighting up when it is stuck in a lemon is a hoax. Because I saw it with my eyes I thought it was real. I am embarrassed; I really should have realised it could not be true. The key feature of a battery [electrochemical cell] is that the anode and the cathode have to be different materials so they have a different electrochemical potential.
But, I think making a real lemon battery would be cool. But it does require 3 to 4 lemons hooked up in series to produce the necessary minimum voltage to light the LED. I want to think about how this could be done in thermodynamics class to illustrate certain important concepts such as the chemical potential.

Friday, June 26, 2015

What is so great about the von Neumann entropy?

I got a referee report for a paper submitted to PhysChemChemPhys that looks at the quantum entanglement of electronic and nuclear degrees of freedom in molecules. The paper goes beyond the calculations considered here, and explores subtle issues about how entanglement may or may not be related to the breakdown of the Born Oppenheimer approximation.

One referee asked a good but basic question, "Why is the von Neumann entropy the appropriate measure of entanglement to consider here?"

Here is my answer. I think experts could do better and so I welcome suggestions.

The von Neumann entropy is widely accepted as the best measure of quantum entanglement for pure quantum states defined on bipartite systems, such as that considered here. This is because the von Neumann entropy satisfies certain desired criteria, including vanishing for separable states, monotonicity (it does not increase under local operations or classical communication between the subsystems), additivity, convexity, and continuity.

It was a bit of work to come up with this answer, because this is all second nature to people who work in quantum information. It is hard to find a place where this is clearly stated and discussed in detail. The Quantiki wiki entry on entanglement measures  and the axiomatic approach, along with the review article by the Horodecki family helps.

Anyone suggest a place where this basic issue is discussed and worked out in detail?

The big challenge is defining entanglement measures for multi-partite systems and for mixed quantum states.

Thursday, June 25, 2015

The tension between accountability and trust

On the one hand I think it is very important that people and institutions should be accountable for their actions. Human nature is such that if people are not accountable they will often choose to act in selfish ways that lead at best to mediocrity and at worst to corruption, exploitation, and waste of precious resources (financial, human, and environmental).

On the other hand, at some level you need to trust people and give them freedom to get on with their job. Too much regulation and oversight can be dehumanising, discouraging, stifle initiative, and also waste resources. For example, the fact that at most universities half of the staff are administrative should be a serious concern.

Consider the following contrasting situations. The levels of accountability and trust are wide ranging.

Sepp Blatter thinks that FIFA should be self-regulating and left to get its own house in order.

CEO's of mining companies will claim that they will "do the right thing" when it comes to environmental protection and the government should reduce regulations.

In one state university in the USA, after one gets a Federal government research grant, one must then undergo an extensive internal review of the project goals, procedures, and budgets. Regular internal progress reports are required in addition to the reports required by the granting agency. Faculty hire administrative staff to manage this process for large grants.

In one department staff and graduate students can use the stationary cupboard, the photocopier, and computer printers as much as they choose. No personal accounts are kept.

I have held grants ranging from $8K to $800K where the reporting requirements were comparable.

In one country a research grant can be spent in any manner and proportion that the PI (Principal Investigator) pleases: postdocs, students, travel, computers, equipment, ...
In another country the funding agency breaks down the budget and specifies exactly what can be spent on each item.

In one university when a PI wants to hire a postdoc, the decision is made solely by them. In another, the PI has to convene a selection committee including the department chair, a faculty member from a different department, and must include gender diversity.

In one university after a faculty member teaches a course they have to file a log showing the content of each lecture and it is checked whether they covered all the material stated in the course profile. At another university no one checks.

At one university if a faculty member wants to take even a single day of vacation it has to be approved by the department chair and logged. At another university no one even keeps track.

Notice how in some of the situations above the institution is clearing trusting people to make the best possible choices. In other situations there is clearly a lack of trust, even in the smallest matters.

How does one find the appropriate balance between trust and accountability?
I am not sure. I would welcome suggestions.

Here are some rough thoughts.

1. The level of accountability should scale with the level of damage that can be done by misconduct.
A mining company clearing thousands of hectares of pristine rainforest is not the same as a graduate student using the department printer to print a gossip magazine article.
I think we actually need significantly more regulation of the rich and powerful and much less of people at the grass roots.

2. Accountability structures need rigorous cost-benefit analysis.
Will the amount of money potentially saved [whether in increased productivity or reduced misuse of resources] be actually be less than the money lost through increased administrative costs, lower staff productivity to reduced morale, inefficient use of resources due to inflexibility?

3. We should be realistic about the limited effectiveness of accountability structures.
The rich, powerful, and gifted are very good at getting around them.
Yet politicians and managers seem to think if they design a new policy, send an email, and require a report everything is going to alright. People game the system.

What do you think? 

Wednesday, June 24, 2015

The challenge of the pseudogap in organic charge transfer salts

I am often sprucing [Aussie slang for promoting] Dynamical Mean Field Theory (DMFT), and particularly how it captures many quantitative details of charge transport and bad metals in organic charge transfer salts.
However, it is always good and important to be transparent about the limitations of any theory, particularly one that you are enthusiastic about.

There is a nice paper
Repulsive versus attractive Hubbard model: Transport properties and spin-lattice relaxation rate 
Rok Žitko, Žiga Osolin, and Peter Jeglič

The authors use DMFT to calculate various spectral functions using the numerical renormalisation group (NRG) as the impurity solver. This is probably, the most reliable method, at least for low temperatures.

There is a lot I found interesting in the paper. But for now I just want to focus on one result in the paper: the temperature dependence of the NMR relaxation rate, 1/T_1.
1/(T_1 T) is proportional to the slope of the local spin fluctuation spectral function
The authors find that in the metallic phase of the repulsive Hubbard model this slope monotonically decreases with increasing temperature. Similar results were found 20 years ago (with a more approximate treatment) by Jarrell and Pruschke.

Why is this interesting?
In the organic charge transfer salts 1/T1T versus temperature is not monotonic, but has a maximum at a temperature (T_NMR) around the coherence temperature, T_coh, marking the approximate crossover from a bad metal (at high temperatures) to a Fermi liquid (at low temperatures). Actual data for a wide range of materials is shown in the Figure below, (n.b. this is a plot of T_1 T vs. T not 1/T_1T) taken from a paper, with Ben Powell and Eddy Yusuf.
That paper also emphasised the discrepancy with single site DMFT.
But, it was good to be reminded of it again.
What is going on?
Basically, like in the cuprates a pseudogap must be opening up. A cluster DMFT calculation, such as this one by Jaime Merino and Olle Gunnarsson [or one by Emanuel Gull ] captures this.
But, it remains to be shown in detail that the NMR data can be quantitatively described and the relationship between the two temperature scales T_coh and T_NMR needs to be elucidated.