Top 5 most cited non-review QM/MM papers since 2010

Concerted O atom-proton transfer in the O-O bond forming step in water oxidation (22 citations)

Solvatochromic Shifts in Uracil: A Combined MD-QM/MM Study (16 citations)

Nonadiabatic Hybrid Quantum and Molecular Mechanic Simulations of Azobenzene Photoswitching in Bulk Liquid Environment (16 citations)

Multiple Low-Lying States for Compound I of P450(cam) and Chloroperoxidase Revealed from Multireference Ab Initio QM/MM Calculations (16 citations)

Inclusion of Dispersion Effects Significantly Improves Accuracy of Calculated Reaction Barriers for Cytochrome P450 Catalyzed Reactions (15 citations)

Excited States in Solution through Polarizable Embedding (15 citations)

At least according to Web of Science: Topic=qm/mm, Timespan=2010-2012.

This work is licensed under a Creative Commons Attribution 3.0 Unported License.

A glimpse of what science is really like: Rosie Redfield's Blog

Nature's ten people who mattered in 2011
Something significant happened as 2011 drew to a close.  The journal Nature named Rosie Redfield one of the ten people who mattered in 2011.  This is significant because she made the list because of her blog, and proved once and for all that blogs are a serious force to be reckoned with in science.

RRResearch
Redfield's blog is a model of open notebook science where data is freely shared as it becomes available.  More importantly, in my opinion, is offers an accurate glimpse of what life is like in academic scientific research: data collection and analysis, writing and submitting a paper for publication, fiddling with software, writing a grant proposal, etc.

The last sentence of the latter post brought another post on another blog to mind: why should blog even if you have no readers.

The fear of being scooped
Why don't we all do this? We are afraid of being scooped: that people will take the data or ideas posted on the blog and write a "real" paper before we can.  Not only is this a rather dim view of humanity and an overly optimistic assessment of the importance of ones research compared to that of others (isn't it pretty trivial if it can be copied with little effort?), it also implies that blogs are not taken seriously as a means of communicating science and I think Nature's top ten list for 2011 has finally proved otherwise.

Anyway, that's what I keep telling myself.

This work is licensed under a Creative Commons Attribution 3.0 Unported License.

PROPKA plug-in to VMD has been released

Michal's PROPKA plug-in to VMD is now included in the latest VMD release.

Where am I sending my next paper and why?

Mathematician Timothy Gowers' recent public boycott of Elsevier has been joined by thousands of other people and I am one of them.

My boycott, mainly because of their support for the Research Work Act (RWA), was not a very courageous move.  I have published exactly two papers in Elsevier journals (both Chemical Physics Letters) and none of their chemistry journals are of the "if only I could publish there" variety in my opinion.

But what about other publishers?  The RWA was supported by the American Association of Publishers of which Wiley and the American Chemical Society are members. If I boycott them where would I send my manuscripts?

Gowers boycott has re-ignited the Open Access (OA) discussion on the net (examples here and here, and this list), where people are grabbling with much the same question.  One journal that is frequently mentioned as an alternative is PLoS ONE, which is an OA journal.  This is where I will send my next paper.  This has not been an easy decision, mainly because of certain "mental blocks" that I struggled with.  Many of these where echoed in the OA discussions and seeing them in print really helped thinking about them rationally. Here I paraphrase some of the arguments as I read them.  My answers to these serve to convince myself to submit the paper to PLoS ONE and are not based on actual experiences yet.

My Usual Journal is more "appropriate" than PLoS ONE for my next paper
"Appropriate" usually means there are many papers like mine there, so therefore it's more likely to be (A) accepted for publication and (B) found by researchers interested in that particular topic.

     (A) I have had papers rejected for two main reasons: the impact was not judged sufficiently high or the subject of the paper was not appropriate for the journal.  Impact is not a review criterion for PLoS ONE and PLoS ONE accepts papers in all disciplines of science.  I admit it is a little unnerving not to see a single "friend" on the editorial board or little more than one or two among the authors, but I think I subconsciously connect this with the "focus" of the journal.  For PLoS ONE there is no "focus" in the usual sense.


     (B) I don't think that's true anymore.  I think most people find papers through search engines.  PLoS ONE is indexed on Web of Science, PubMed and Google Scholar.  I certainly don't peruse the table of content of a single journal anymore.

PLoS ONE is not prestigious enough and publishing there will hurt my career
My next paper would have gone to Journal of Physical Chemistry A or Journal of Chemical Theory and Computation.  I just don't think these journals are more prestigious than PLoS ONE.  This is a judgement call and I'd be happy to hear opposing views.  All three have similar impact factors.

If I thought my next paper had a shot a Journal of the American Chemical Society, I am not sure what I'd do, but it isn't (it's a method development paper).  This post is not to announce an ACS boycott.  It is about where I am sending my next paper and why.  One paper at a time.

A publication list with most papers published in one journal (PLoS ONE) will hurt my career
This argument is usually rephrased as "there aren't enough OA journals in my field yet".  Since PLoS ONE accepts papers in any scientific field I can only assume they feel uncomfortable sending most of their papers to PLoS ONE.  My specific response is: if my paper gets accepted I'd have exactly one paper published in PLoS ONE, so this is not an issue now.  One paper at a time.

My more general response is: If all your papers are in Nature your career is not in jeopardy.  However, if all your papers are in Journal of Very Specific Research it could look like your work is not of general interest and that you don't collaborate with anyone.  However, since PLoS ONE publishes in any area of science these are not valid arguments here.


I can't afford the $1350 publication fee for PLoS ONE
There is an automatic fee-waiver.  The request for the fee-waiver is separated from the review process and will not impact acceptance.  Anyway, I have the money this time, so it's not an issue.  One paper at a time.

PLoS ONE is not peer reviewed
Yes it is.

PLoS ONE does not publish reviews
I have actually seen this argument brought up in these kinds of discussions!  Anyway, my next paper is not a review so that's irrelevant. One paper at a time.

Right, that's me convinced!  Now I just have to tell my co-authors ...

First announcement: Electronic Structure Theory for Strongly Correlated Systems

==================
FIRST ANNOUNCEMENT
==================

ELECTRONIC STRUCTURE THEORY FOR STRONGLY CORRELATED SYSTEMS

In celebration of Per Ake Malmqvist' 60th birthday and his career dedicated to quantum chemistry.

May 30 - June 1, 2012
Palermo, Italy

http://www.teokem.lu.se/PAM60/

Important deadlines: 
March 1st, 2012 - early-bird registration 
April 15th, 2012 - deadline for abstract submission  

Registration: http://www.teokem.lu.se/PAM60/registration.html
Note that the number of participants is limited.

For more information please, contact Valera.Veryazov@teokem.lu.se

Energy transfers to maximize entropy: a lesson from Molecular Driving Forces

This is Figure 3.14 from Dill and Bromberg's Molecular Driving Forces, which is my favorite book on statistical mechanics.  It is a beautiful example from a beautiful book.

If you haven't already, it is a good idea to read Illustrating entropy and Where does the ln come from in S = k ln(W).  Go ahead, I'll wait right here.

System $A$ has an internal energy $U_A=2$ which is distributed among the 10 particles in $$\frac{10!}{8!2!}=45$$different ways.  Similarly, System $B$ has an internal energy $U_B=4$ which is distributed among the 10 particles in 210 different ways.

If the two systems are allowed to exchange energy, what is the most probable distribution of energies?  It is the one for which $$W_{total}=W_AW_B$$ is largest.

Now compute $W_{total}$ for three cases: no energy transfer ($U_A=2,U_B=4$), one where energy is transferred from $A$ to $B$ ($U_A=1,U_B=5$), and one where energy is transferred from $B$ to $A$ ($U_A=3,U_B=3$).  If you don't have a calculator handy, try Wolfram-Alpha.  Which state is the most probable?

     

Energy transfers to maximize the total entropy, not equalize energies
The most probable state has the largest total entropy since $$S_{total}=k\ln(W_{total})$$In this particular case maximizing the entropy leads to equal energy, but that is only because the two systems have the same number of particles. Consider system $A$ in the figure above in thermal contact with system $B$ with the same energy ($U_B=2$) but only four particles.  What is the most likely state? (Don't guess, compute!)

     

Maximizing entropy, means equalizing temperatures
It should be clear by now that if you change the internal energy, you change the entropy$$dS=\left(\frac{\partial S}{\partial U}\right)dU$$This is actually just the thermodynamic definition of entropy $dS=dq_{rev}/T$ which means that$$\frac{1}{T}=\left(\frac{\partial S}{\partial U}\right)$$When $S_{total}$ is a maximum the change in total entropy is zero, so $$\begin{aligned}dS_{total}&=dS_A+dS_B\\&=\left(\frac{\partial S_A}{\partial U_A}\right)dU_A+\left(\frac{\partial S_B}{\partial U_B}\right)dU_B\\&=\frac{1}{T_A}dU_A+\frac{1}{T_B}dU_B\\&=\left(\frac{1}{T_A}-\frac{1}{T_B}\right)dU_A\\&=0\end{aligned}$$Here I have made use of the fact that the total internal energy is conserved$$dU_A=-dU_B$$

That's Classic!

I've very recently had the joy of setting up classical simulations for use in my research developing the next generation of force-fields. Since I've dealt with quantum mechanics and classical mechanics derived from quantum mechanics, my need for classical simulations on proteins and ligands has been void. Until now.

I only know of two tools to actually calculate Molecular Dynamics simulations on entire proteins: The Tinker package and the GROMACS package. I've tinkered(!) around with the first package and kept a good distance to the latter, but times have changed since I needed to include a ligand. GROMACS (and Tinker for that matter) are tuned to either proteins (in solution) or small molecules (in solution)*. If you want another molecule to use for the MD, you must first obtain the force-field parameters somehow. Since the most of us have no time for that, or that the next generation force-field is on its way but not quite there yet, what do you do?

To start from nothing and finish two days later, I did what any (in)sane scientist would do if no-one in the department has apparent experience with a particular piece of software: I Googled and I browsed the GROMACS "guides". The first is good if you know what to look for, and the latter is good to get inspiration, but it does not quite get you there since information always seem to be outdated just a bit.

Here is how I did it:

1. Find the structure of interest to you on the Protein Data Bank. Build your ligand into that system using your favorite build tool. You should now have a PDB file with a protein and a ligand.
2. Use SwissParam (more info below) to make a topology file (actually it is a force-field) of your ligand.
3. Follow the SwissParam Gromacs guide until step 6 (you must include this step!)
4. Follow the Protein-Ligand Complex guide by Justin Lemkul from the solvation step (it is good to actually read the entire guide). This will get you to make a production run MD of 1 ns of your own system.
5. Analyze your MD! This is out of scope for this post, but man was I happy when the MD actually successfully finished.

Note on SwissParam
The SwissParam tool takes a small molecule of interest and generates what is know in GROMACS-speak as a topology file, but in regular office-chatter, this is known as a force-field. Here is an exert from the main page of SwissParam

The data are derived from the Merck Molecular ForceField (MMFF). Dihedral angle terms are taken as is, while only the harmonic part of the bond, angle and improper terms are retained. Charges are taken from MMFF. Van der Waals parameters are taken from the closest atom type in CHARMM22.

The paper of SwissParam(doi:10.1002/jcc.21816) has been published so give it a read if you're really feeling geeky.

* I should note that if one chooses the MMFF 94 force field in Tinker, one should potentially be able to use it for everything, but it is a bit messy to actually set up and run not to mention that I found absolutely no way to automate the atom type-setting.