Louisiana Kitchen

BPS17 is already over, and I had a lot of fun!

I met new people, had time to catch up with my friends and learned a lot from the posters and platform sessions. I also enjoyed the reception on Monday. The band at the quiet room was very nice! They even played a Brazilian song (Girl from Ipanema). I just wish there were more free drinks.

I thought I would not enjoy the food in New Orleans and planned to not write about it. But I am happy to say that I was wrong. I really enjoyed the red beans and rice. It reminds me of Brazilian food, with a different seasoning. I also had gumbo, a sort of stew made of meat or chicken and served over rice, for lunch during most of the conference. And I am planning to try catfish soon.

Now that BPS is over, I will spend some days sightseeing in New Orleans. Today I had time to follow some tips of a previous post, walk along the Mississippi River and listen to some jazz. If you like jazz, I recommend you a bar I went today, BMC. It is on Decatur Street at Esplanade. The band playing today (Wednesday) was very nice and there is no cover charge there. Walking along Decatur Street was also awesome! There are many old buildings with balconies, which reminds me of Paris. The name French Quarter for this neighborhood really makes sense.

How can we quantify entropy?

Entropy is one of the most interesting concepts in physics. If we define a state as a group of protein configurations separated by low energy barriers (~ 1 kT), we can relate entropy to the number of configurations of this state. The higher the number of configurations, the higher the entropy of this state.

Jose Caro, during his presentation at the Protein Dynamics and Allostery platform session on Sunday, presented a very interesting proposal to quantify entropy changes from experimental results. According to his presentation, most contributions to the entropy of a state come from protein motions in the picosecond timescale. This motions, in turn, can be detected by nuclear magnetic resonance (NMR) relaxation. A high order parameter (close to 1) indicates a rigid protein, while a low order parameter (close to 0) indicates a flexible protein. His idea was to quantify entropy changes by scaling changes in the order parameter.

The poster section on Sunday was also very interesting. I had very nice discussions, and among them I highlight my conversation with Carsten Kutzner about the computational electrophysiology method. He is pretty passionate about his work at the Max Planck Institute for Biophysical Chemistry.

The poster section of today (Monday) was awesome! I met some former lab mates and friends from my six-month visit to the University of Pittsburgh last year, met a friend from a Gordon Conference, and also met totally by chance professor Alex Dickson, which has been doing a really nice work on pathway sampling.

The bad thing is: my networking cards from Quartzy are over. Quartzy, would you make me 20 cards next time?

What are the challenges in the simulation of ion channels and transporters?

I arrived at New Orleans on Saturday and had the pleasure to watch very good presentations at the Permeation and Transport Subgroup session.

Molecular dynamics (MD) simulations of any system involve some approximations, like the use of classical mechanics instead of quantum mechanics to describe the time evolution of the system, or the representation of atoms with fixed point charges. The lectures of prof. Jana Shen and prof. Sergei Noskov (link) at the Permeation and Transport Subgroup session on Saturday employed methods to overcome some of these approximations.

In conventional MD simulations, the protonation states of titratable groups are attributed based on pKa values obtained from experimental conditions that usually do not resemble the conditions of these groups in the protein structure. Moreover, once assigned the protonation state is fixed for the whole simulation. Prof. Jana Shen highlighted that such approximations can lead to incorrect protonation state assignments, neglect of coexistence of the deprotonated and protonated states for a given pH and fail to offer mechanistic insights where changes in the protonation state matter. To avoid these approximations, prof. Jana Shen used in her work continuous constant pH MD (CpHMD) simulations, a type of simulation where the protonation state of a titratable group changes according to the environment. Using this method, she was able to reveal molecular details of the mechanism of Na+ transport in the NhaA antiporter.

Prof. Sergei Noskov showed in the beginning of his presentation that the presence of a divalent ion inside the ion channel pore can modify the electronic structure up to the second solvation shell. This result was obtained by quantum mechanical calculations. In conventional MD simulations, on the other hand, atom charges are fixed, and polarizability effects as those caused by the divalent ion would not be accounted for. To include polarizability in MD simulations, prof. Sergei Noskov employed a drude model, parametrized by him and co-workers, to describe his system. In the drude model, each atom is represented by two charged particles attached, what allows some change in the charge distribution of a single atom. He showed some pathways for ion permeation in NavAb and CavAb channels , and that some stable configurations identified by MD simulations with the drude model were missed by classical MD simulations.

MD simulations have many approximations, and whether we need to avoid them or not depend on the question we want to answer. The two lecturers above wanted to answer questions that required improvement of some of the current approximations, and they were able to employ methods for higher quality modeling to answer their questions successfully.

Are you ready for BPS17?

My preparation for BPS17 started since August last year. I’ve been working with molecular dynamics simulations during my PhD, and decided to look for a postdoc position to work with simulation of ions channels or membrane proteins. I read some articles from different authors in the field and chose the PIs whose works interests me the most. I contacted them on the beginning of January and scheduled some interviews for BPS17.
Moreover, I have been working on my presentation for BPS17 since the beginning of January. I was selected to present in a platform session, which allots 15 minutes for presentation and discussion. Making a presentation for such a short time is tricky for me, because the talk may contain only the most important information of the work and, at the same time, it must show a compelling story.
Now I just need to pack my case for the winter in New Orleans and look at the Desktop Planner and choose the lectures I will attend.
If you haven’t looked at the Desktop Planner, I strongly suggest you to do so, because there are many interesting lectures happening at the same time. And if you are in the end of you PhD like me and planning to apply for a postdoc position or a job in industry, take a look at the workshops of the Career Development Center. They are covering a range of topics, from networking to career options beyond the bench.

See you in New Orleans!