Producing reliable science

Have you guys recovered from the national lecture yet? I definitely haven’t!

I use the phrase “recover” for a reason. What struck me in the lecture was this realization: we never study cells in their native environment!

It struck me for two reasons. One, it’s scary. Second, how come we never thought of it? We know it from our undergrad years that when you strike an object with a photon, you perturb it. When you perturb something, it is no longer in its native state. It’s really that simple, yet it took me all these years to realize that. And scary because….well……in the words of the speaker himself, “seeing is believing, but how can I believe what I see?”

Producing reliable science was the theme at most of the sessions I attended today. The ones I enjoyed the most were talks about development of force field parameters for molecular dynamics simulation. Force field parameters govern the strength of various interactions between atoms in a simulation, which in turn has significant effects on what we see in the simulation. Force field parameters need to be accurate to reproduce experimental data, and an enormous amount of effort is spent to improve this accuracy.

The first talk of the “Molecular Dynamics I” platform was by Paul Robustelli, from the David Shaw Research group. This group developed and maintains Anton, the most powerful supercomputer dedicated to molecular dynamics simulation. The talk focused on one drawback of the existing force field: no single parameter set accurately describes both ordered and disordered states of proteins. The Shaw Research group is solving this issue by modifying the way dispersion interactions are defined (for the mathematically inclined: we are talking about modifications to Lennard-Jones potential). With the power of Anton, their team has verified the new parameters on 20 different proteins.

The next talk, by Sarah Rauscher, described similar improvements to the CHARMM force field. CHARMM is one of the most widely used force field among biophysicists (our group included). CHARMM’s latest version, CHARMM36, had been showing something unexpected: it was favoring left-handed helices much more than what was observed experimentally. Dr. Rauscher described how their group went on to find out the source of the problem, and the results they obtained after fixing the same. The new CHARMM36m force field has much better agreement with the experimental structures, and has taken us a step ahead towards believing what we see.

Before signing off, I would like to remind you: I am presenting my poster tomorrow at poster board B536. If you want to know about exploiting tumor acidity for treating cancer and/or implicit solvent simulation of peptides to study helix-coil transitions, feel free to drop by.


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