For the last few days I have been trying to figure out how I can do a simple Monte Carlo simulation on my computer without much success.

In the last few months I have become convinced that by doing my own computer modeling I could probably avoid making a lot of unnecessary molecules.  Indeed, I see no reason why the notion hasn’t struck me in the same way the concept of checking a sample after a reaction for purity why should I check the reaction before I do it to see how well it might work?

Firstly, it’s become pretty obvious that computational chemistry is a giant fucking black box.  There are lots of force fields and data sets and letters followed by ** and shit and not a goddamn easy way to deal with ANY of it.  Let’s say I want to model a transition state, what do I do?  Call a computational chemist?  I’m sure they’ve got shit they want to do, too.  Not only that, but after a couple decades of ripening, I’d like to think the ability to do simple computational analysis should be in the hands of the average schmuck like me.

So, I want to do a Monte Carlo simulation.  This, as I have come to appreciate it, simply means I want to find a global minimum for a structure – i.e. the lowest energy configuration something sits in, but there’s no easy way to figure out how to do this.  In so far as I can tell, you can do the following things:
Draw something in chemdraw and either import it into Chem3D if you own a PC or into Avogadro if you own a Mac (which will convert chemdraw .cdx files into 3D coordinate files).  Do a minimization using whatever they have.  Avogadro is clearly better at this (and it works for PC) and has a number of different choices.  The problem with both of those program is that they really don’t find a global minimum.  Insofar as I can tell, if you start with a shitty structure, both of them will find a minimum of that shitty structure.  True Monte Carlo, as I understand it, means it will rebuild the structure and keep searching.

Then I discovered a program called Tinker… it has a bunch of force fields and shit in it, all prime and ready to use (and it even works on Windows and Mac) but no clear path from Avogadro or Chem3D to a minimization is presented.

I don’t understand why computational chemists don’t want other chemists to do computational chemistry with a graphical user interface and dialog boxes and all those smart things that can be made using Visual Basic or Apple script… It just seems to me that, a lab like Jay Ponder’s or Dan Gezelter’s could really make a difference by making a user application that would allow the simple importation of a Cartesian coordinate file and allow the user to select a Force Field, Algorithm and a good stopping point to do their own “back of the napkin” calculations before they run off into the lab…  If I had the wherewithal to do it, I’d have done it by now.

UPDATE:  Re: Collaborate with a computational chemist:

I have done that before, put his name on the paper and everything.  The problem is that I’m *JUST* starting out in my little Post-Doc adventure and so I don’t really have systems in mind that I would want to bother someone with.  I.E. some of them are likely patently absurd – simply won’t work for reasons I don’t need a computer to tell me… but I have a chemdraw folder full of them and a billion other (more pressing) things to be doing.  I also have a pretty ass kickity computer that has no problem crunching numbers all day, both at home and at school.

I also want to obtain some degree of self sufficiency.  I feel as though, in this modern era, I don’t need to run to an NMR chemist to take a sample of, what will normaly turn out to be ethyl acetate, so why should I need to run to a computational chemist to do something so very trivial.  It’s a waste of her time to do my calculations for me on a compound that has a 1% shot of even being made!

In a recent PEW report, scientists rank roughly equal to doctors (those are “real” doctors) and slightly less than teachers in the public’s eye.  In other words, if the public had a giant T-Mobile cell phone their fave-5 would be Military>Teachers>Scientists>Doctors>Engineers.  This is a good thing, I suppose, but I still don’t think we’ll be getting discounts on cars or preferred air travel.

On the other hand, 85% of scientists think the public is full of retards and 50% feel as thought the public has unrealistic expectations of what scientists can do.  I quoth:

While the public holds scientists in high regard, many scientists offer unfavorable, if not critical, assessments of the public’s knowledge and expectations. Fully 85% see the public’s lack of scientific knowledge as a major problem for science, and nearly half (49%) fault the public for having unrealistic expectations about the speed of scientific achievements.

Then there is a section for bellyaching on the lack of funding…

If you follow down that long list of questions two things popped out at me:

87% of scientists believe in natural selection compared to 32% of the general public.  I’m concerned about that number.  87%? 1 out of 10 scientists think God did some magic shit?  hmmm… That’s a fucking shame.  I’d accept 95%, just because people are weird and there’s nothing you can do about that but 87% seems awfully low.  While I can dismiss the public as being horribly educated (thanks teachers – who are more loved than us!) and thus more likely to reject something that has been horribly explained to them, I have a hard time doing the same for quote-end-quote scientists.  Coincidentally, roughly the same number (84%) think the earth is getting warmer due to man’s involvement.    At the very least, we can all agree 84% is a consensus, since, apparently, 13% of “scientists” haven’t yet discovered the first chapter of a biology textbook.

Then, at the very bottom, the partisan breakdown occurs with an astoundingly low 6% calling themselves Republican (so shut up Bill Carroll) with a slightly higher number (9%) calling themselves conservative. (I think they’re mostly engineers.)

Since starting my postdoc no less than 45 days or so ago I haven’t really commented on the subject, though I think I can now comment on, at the very least, the first 3 days (what with having all this time to reflect upon them and all).

The position of a post doc is a confusing one, to say the least.  You’re really not that much better than a 4th or 5th year graduate student, despite having additional initials after your name and, if you didn’t fuck up, you’re probably at a bit more of a competitive lab or a more impressive school (or it was, at the least. a lateral promotion to something equivalent.)  Either way, the people around you are fucking smart and ready to take you and everyone else on intellectually.  Now is not the time, of course, to retreat into your shell… this would be a mistake.  Instead, you have to toss yourself out there as simultaneously self assured and humble.  It is the postdoc, after all, that crashed into the delicate ecosystem of the lab and as the guest I find myself silently listening to world around me.

What is this madness that I have begun?  A group 3 fold larger than the one I left, I find each of us (that is, all the members) attempt to be unique snowflakes with varying degrees of success.  The office layout is horrible – the separation of the lab into multiple offices in different hallways has lead to apparent cliques and associations.  While, granted, my former lab was separated by floors, we were always close.  If I were to, say, go out to lunch with some of my group members, trash talking was more along the lines of “if so and so doesn’t get their shit together they’re going to fucking piss me off” and not so much the “I’m going to fuck so and so in the eye socket in front of her children.”  The cordial flavor of a provincial department has given way to the cutting edge of brutality.  I’m ensconced in brilliance, laziness and madness all at once and am supposed to be a leader of this ragtag crew and, while there is a clear thirst for knowledge and a love for science, there is also a dynamic that eludes me.  Make no mistake:  it’s a super group of the highest order and it’s sink or swim; I’m happy to be here and love everything going on around me but it’s overwhelming – daunting even, fuck… I can’t even remember everyone’s names.

So I sit quietly waiting for the first years to filter through, hopefully I can catch some of them and convince them to follow me on my own wild scientific quest for the latest in high science and high praise.  For now, I’m focusing on doing something major – a novel innovation.  It’s unbelievably difficult to come up with something novel, I appreciate that now, particularly when you have to keep it in the context of what the scope of the lab is doing.  I have some ideas, but they’re not ripe enough to pick from the tree…

So I sit, reading the literature for 10 hours a day… waiting for inspiration to strike me.

I hope it strikes soon…

UPDATE:  It struck.  And I’m off to the races…

The US supreme court ruled a few weeks ago that the chemists that perform tests in forensic analysis are not immune from cross examination by defense attorneys.  It’s not surprising that the American judicial system did not inherently allow for this, since it’s a very biased and fucked up system.  With this tool in the briefs of attorneys, it sets up a very real and very likely chance that a number of methods used in forensic science, as conducted in the state crime labs, will not hold up to scrutiny.  Not because they’re necessarily invalid (though, we shall see about that), but because they’ve not been done with the appropriate controls – an argument mentioned in the majority arguments by Scalia:

He cited one report, for example, that said “there is wide variabiility [sic] across forensic science disciplines with regard to techniques, methodologies, reliability, types and numbers of potential errors, research, general acceptability, and published material.”

Putting the chemist or lab technician on the stand to be tested by cross-examination, the majority said, will help “weed out not only the fraudulent analyst, but the incompetent one as well.

While this is a good thing for people who are accused of crimes they didn’t actually commit, it provides a way for a young, naive lawyer to get unfortunately schooled in a cross examination.  Without knowing the fundamental questions one should ask (and know before you ask) this could be a strategic blunder, making the forensic evidence look all the more compelling.

So, then, what should a young lawyer who suddenly learned they have this new power look for?  Frankly, I don’t know – but I can say there are somethings they should be aware of:

TLC (thin layer chromatography) is not a quantitative method because commercially obtained plates do not contain a consistent density and quality of silica, which means any TLC results are suspect without a co-spot.  Even so, co spotting can be misleading, unless you’re using the correct visualization method, to make sure you don’t have any overlapping spots.  In effect – I’d thing TLC evidence would be the easiest to toss out and make fun of as a method to corroborate a story.  It may be good enough to test purity for a rough guess, but it’s not accepted in the journals as proof – because it’s not.

MS  (mass spectrometry) can be misleading since calibration of the instrument must be done correctly.  Any competent technician will give the method of calibration.  I would guess that state labs use old equipment and they very would could be passing off aberrant noise as a peak of some sort.

Actually, I have to assume most of the stuff they’re doing is done on really old equipment – though that in itself isn’t reason to suspect the results.  Questions regarding the validation of that equipment, however, is appropriate.  Most scientific instrumentation loses some degree of precision as it ages, rendering it less accurate at the extremes of its detection ranges.  External companies are often used (and are usually necessary) to validate the instruments to some specification (I assume NIST standards) and provide proof of that validation.  Equipment that lacks this validation may not necessarily provide reliable evidence.  If a case could result in a very long incarceration of someone who may be innocent, the calibration – even in a reasonable range of detection, should be a concern.

GMP protocols probably will provide a better guide than I could.  I assume if it’s a standard by which drugs are made, it should be a standard by which evidence is measured….

One of the most confounding things I have discovered is how horrible some of the smartest people I know write.  While they can effectively spin yarns on the research they do with both clarity and poise yet they cannot put pen to paper and produce a single cogent product worthy of reading.  The single gravest sin, as I see it, is that they write like they speak and have no sense for punctuation.

While it’s probably too late to teach grammar, it’s never too late to convert someone’s hideous writing style to something more in line with a readable manuscript.  Allow me to suggest a few cardinal sins in writing a scientific paper, if I may:

1. Using similes and metaphors.
2. Writing in the passive voice.
3. Switching verb tenses.
4. Using unnecessary words.

Each of these rules, in particular the first one, are inviolable offenses.  The first one, of course, is self explanatory.  There should be no reason to use a figure of speach since they do not translate well and are usually corny.  The other three, on the other hand, require a bit of ‘esplanin.

The active voice in scientific writing can be difficult because it requires you to overcome a rule which was ingrained at some point into your head: the use of pronouns.  I had to go back and check if this advice was kosher with the Whitesides’ method and it appears as though it is – surprisingly.  The sentences taken:

Passive: It was observed that the solution turned red.
Active: We observed that the solution turned red.
Sexually Active: I fucked the solution until it was red.

Writing in the active form, while it may force a pronoun every here and again, forces you to keep your sentences short and to the point.  Alternatively, that sentence could have simply stated:  The solution turned red.  The fewer words, the better (if I may generalize) almost to the point that you’re generating paragraphs of bullet points.  After all, the point of a scientific document is to state all pertinent details in a readable narrative.

Verb tense somehow gets fucked up every now and then, even in the hands of seasoned writers.  As it typically happens, multiple drafts end up with multiple tenses and before you know it you have added a reagent in both the present and past tense.  How can I really do more than tell you to avoid it?  I dunno.  Just try.

Using unnecessary words is as noisome as it is common.  “For instance,” “also,”  “additionally,”  and “then” are added to sentences for no apparent reason.  Let me give you an example of a sentence:

In order to look at the binding of substrate 1 we initially studied the spectra of both uncomplexed and complexed substrate and then preformed a titration on both substrates at room temperature to give a Kd of 3.1 nM.

Too many fucking words.  Allow me to truncate:

After analysis of reactant and product spectra, titration of substrate 1 gave a Kd of 3.1nM at room temperature.

DONE.  In the top sentence, some of those words are screaming “DELETE ME!”  “In order to…” is meaningless and look, a superfluous “then!”  Why?  Why fill your sentences with so much shit when you can have such a nice pretty sentence that says everything you want it to.

The problem with effective writing is infrequently the use of too few words.  To the contrary, it is using too many which have no point.

Adjusting is painful. In fact, it’s not going well. Not so much to the group or the research, that’s fine; adjusting to my new world, however, is harsh and I think I’ve gone and changed too many variables all at once.

The first bona-fide problem I have faced is the process of acclimating to a new neighborhood. My wife and I are one of the very few white people that live there and I find myself confronting ugly prejudices in myself and my neighbors that I didn’t realize were there. I considered myself a pretty open minded individual, even minoring in Afro-American studies (99% of you are now confused) and doing the whole ‘we should be multicultural’ and shit and I did it all from my cushy lofts in my bay area setting… but now… erm… I don’t really want to fucking be multicultural. I want to sit around with a bunch of white people at Starbucks and talk about how we should be multicultural.

It’s not a ghetto, really, it’s pretty clean with lots of parks and green spaces… I mean… that’s something to deal with. I’m also personally unhappy with myself for being so uncomfortable around black people who actually wear baggy white tee-shirts and do-rags and hang out on street corners playing hip hop and their parent’s don’t have a Master’s degree and drive a BMW.

Also, I can’t find SHIT.

So, in closing:

Black people make me nervous.

I can’t find anything in the lab.

As a function of my new post-doc, I found myself in the need of a refillable fountain pen, which could contain organic solvents. It also needed to be refillable by a plunger or cantilever and, once I was done with the science, I wouldn’t mind converting it to a nice pen for my own use.  (You may be wondering, wtf kind of chemistry are you doing where you’d be using a fucking FOUNTAIN PEN?  To wit:  I am doing awesome chemistry.)

In any regard, I have (as most scientist do) an inexplicable compulsion (it has nothing to do with masturbation, just FYI… I know that’s a common one.)  My compulsion happens to be the exclusive use gel pens. I thus figured, if I’m going to get a refillable fountain pen, I might as well inquire into the availability of that gel ink they use in gel pens. (It’s not really available…)

Of course, at the time, I didn’t know what made them so gel-like and why I loved them so… but regardless, now I appreciate that I can feel much safer knowing that the federal government can’t track my ink. (DOI:10.1111/j.1556-4029.2006.00144.x)

As every Republican can tell you The Federal Government has been evil for at least the last 3 months – ever since Glenn Beck started warning you that “they” are coming for your guns and your personal rights and your Fieros and whatever redneck accoutrement that you find so appealing yet have parked out on your lawn.  What you may not know is that the feds have been keeping a meticulous database of inks since the 1920’s and at ANY TIME they could take your ink and compare it to their stock samples of ink by… wait for it… TLC! (oh noes! blow up teh fedural buldins!)

Srsly.  Co-spotted and everything.  The fucking FBI will compare ink composition by how far the little constituent dyes run up a TLC plate:

TLC is one of the most widely used and generally accepted scientific methodologies used to compare and help characterize ink formulations. TLC has been discussed extensively by Witte (21), Brunelle and Pro (22), Brunelle and Reed (23), Brunelle and Crawford (24), Kelly and Cantu (25), and Aginsky (26). TLC analysis begins by removing an ink sample from a document, and subsequently extracting the ink in an appropriate solvent. The extract is then applied to a specially coated TLC plate (e.g., glass or plastic surface coated with silica), and placed in a solvent-equilibrated glass chamber containing a solvent or mixture of solvents. The sample components then migrate up the plate via capillary action. Typically, the colorants (e.g., dye components) that are present in the ink sample will separate into colored bands or spots. As described in the aforementioned study conducted by Roux et al. (20), ‘‘thin layer chromatography had the highest discriminating power for the individual techniques at 0.98 for blue and 0.99 for black.’’

I know, I know… we sent fucking human beings to the moon 40 years ago and we still don’t have one of those fantastic neon lit LC/GC/MS/Magic box from CSI that spits out the type of ink and where it was purchased.  But fear not, they can (and will) track your shit down with the almighty TLC plate…  unless… you use gel pens.  Turns out gel inks are poorly soluble in the highly polar solvents they use for TLC (EtOAc:EtOH:water in a ratio of 70:35:30… not a typo… [these people fucking solve crimes]). While most pens contain inks that are water soluble or organic soluble – gel inks contain both, plus some insoluble pigment shit.

The Gelly Roll, a name which could only be dreamed up by the psychotic lotus eating scientists of Japan at Sakura Color Products Corporation was the first gel pen invented in the mid 80’s and contains water and oil based inks dissolved in an aqueous mixture thickened by xanthan gum and pigments suspended therein.  Fountain pens and rollerball pens use water based inks while ballpoint pens use organic derived dyes.  Thus, the inherent insoluble nature, as well as the broad range of polarities in the gel pen resulted in EPIC FAILS:

The colorants in 15 of the writing inks did not extract into solvents and/or migrate on the TLC, which indicates that they are pigment based. These inks were not feasible for comparison with the library of standards based on their lack of a colorant profile on a TLC plate; however, this would not preclude additional comparative testing using alternate methods such as Fourier transform-infrared spectrometry (FT-IR), gas chromatography-mass spectrometry (GC-MS), liquid chromatography-mass spectrometry (LC-MS), and/or scanning electron microscopy (SEM) coupled with energy-dispersive X-ray analysis (EDXA). It is noted that 14 of the 15 inks that were not extractable were gel inks [...]

I am pleased to know that the feds will be unable to know where I purchased my ink.  That’s one more “freedom” I can keep. (I purchased them at Sam’s Club. Great fucking deal. I got, like, 50 of them for $40.)

Derek’s recent blog posts, have forced a bit of reflection in me on the  “Chemistry fatigue” often felt by people who file in and out of college classrooms.  The chemistry they encounter is not the chemistry the world does.  The way chemistry is taught in collegiate settings is not the way chemistry is taught in the lab.  Chemistry pedagogy is to blame – often antiquated methods of teaching chemistry with no obvious purpose would (and should) lead anyone to surmise that the subject is (1) hard (2) academic and unpractical and (3) used more to “weed out” kids from premed programs than to teach them fundamental skills on problem solving that will help them later in life.

For instance, not but 9 years ago my chemistry lab course, which was taught by a pioneer in alene chemistry, contained only compound characterization labs using chemical elucidation techniques.  (Tollins, flame tests, etc…)  The class was not useful for me as a chemistry major and it was undoubtedly less useful for those that were taking it for their own purposes.

While the ACS has done their bit to fill the airwaves with “chemistry touches all our lives” commercials, I’m not entirely sure they were effective.  When I sit down to read SciAm, there may be one article devoted to chemistry with a preponderance of bullshit on the latest paradigms used to explain the nonsense of deep space tissue penetration and the obligatory article on some cloned or transgenic critter.  There isn’t much of a market on the wonders of chemical magik; even the more user-friendly chemistry that comes prepackaged with pretty pictures like those out of the labs of Stoddart, Rebek and Anslyn get no attention.  Somehow the uselessness of the deep mysteries of invisible matter in the cosmos is more compelling than the efforts of man right here on Earth.

There may be an absence of a strong voice.  Physics did have charismatic men like Carl Sagan and Richard Feynman who were relentless advocates for science education of the masses.  I have heard suggestions of Carolyn Bertozzi being such an advocate, and I myself could think of few more capable, but hitherto, I have not seen her advocate for chemistry on a national scale, though her advocacy on behalf of women in science and the GLBT community in general has been highly admirable.

So, what’s to be done?

I wonder if the time for a Carl Sagan like figure to appear to children and mesmerize them with a soft voice in their living rooms is passed its time.  Back in the day, we watched PBS because that was one of 10 channels, unless you were lucky to grow up with cable (I wasn’t), it was PBS or daytime soaps.  There are entertainers like Bill Nye, but advocacy for science in general doesn’t really help the cause of making chemistry more accessible, even though it can’t hurt.

In short, I feel as though the problems are many and splendored.  Everything from a lack of advocacy (which has lead to ignorance), to poor pedagogy from high school through college has shaped chemistry to be the monster and bane of premeds and premed dropouts alike.  The subject isn’t inherently easy, but I’d wager it’s no more difficult than physics (if physics were easier, I assume I’d have gone into that) and I’m not suggesting making it dumber (though, I question the amount of sincerity with which it is taught – sophomore organic chemistry should not be the intellectual gate through which all must pass before getting their membership to the Intelligentsia.)

I will choose from the top candidates on the basis of URL availability (or, if it comes down to it, preference).  You choose your two five favorites and I’ll sort out the rest.

Fucks sake there are a lot of people in my new group.  I can’t count them all – over 30, I’m sure.  I think most of them are Post-Docs…

When I started teaching as a graduate student I took the time to learn all my students names – the first semester.  By the last semester I taught, I knew about exactly zero names in my lecture.  I’m not so good with names and I’m not so good with getting to know people.  It’s a huge pain in the ass but everyone seems to be friendly enough so far.  Haven’t gotten the “new guy from a shitty lab” feeling yet.

I’ll get to the wiki in a bit.  It’s doing much better than I had thought it would.  I may move it to this server sooner than I had thought, since the amount of data I can store on their server is limited to 50 MB for free accounts.  I also discovered that “Common Chemistry” was already taken by CAS, so I need another name.

Please suggest names in the comments below – We can do a vote and I’ll send the person who wins a free cup from The Chemblog store.