Peptide Springiness By Terahertz Spectroscopy – An Upcoming Cover For Angewandte Chemie (And A POV-Ray File For Generating Springs)

image_m_anie201603825-toc-0001-m

From: onlinelibrary.wiley.com/doi/10.1002/anie.201603825/full

Image caption: An approach combining terahertz spectroscopy, X-ray diffraction, and solid-state density functional theory was utilized to accurately measure the elasticities of poly-l-proline helices by probing their spring-like vibrational motions. In their communication (DOI: 10.1002/anie.201602268), T. M. Korter and co-workers reveal that poly-l-proline is less rigid than commonly expected, and that the all-cis and all-trans helical forms exhibit significantly different Young’s moduli.

Article: onlinelibrary.wiley.com/doi/10.1002/anie.201602268/abstract

Abstract: The rigidity of poly-l-proline is an important contributor to the stability of many protein secondary structures, where it has been shown to strongly influence bulk flexibility. The experimental Young’s moduli of two known poly-l-proline helical forms, right-handed all-cis (Form I) and left-handed all-trans (Form II), were determined in the crystalline state by using an approach that combines terahertz time-domain spectroscopy, X-ray diffraction, and solid-state density functional theory. Contrary to expectations, the helices were found to be considerably less rigid than many other natural and synthetic polymers, as well as differing greatly from each other, with Young’s moduli of 4.9 and 9.6 GPa for Forms I and II, respectively.

With thanks to Prof. Timothy Korter and Dr. Michael Ruggiero for letting me flex some rendering chops (and extra to Tim for knowing what he wanted to see early on).

The cover (well, a cover – they cram quite a bit of artwork into their journal nowadays) for this month’s Angewandte Chemie highlights the correspondence between mechanical spring motion and the excitation of small alpha-helices by terahertz spectroscopy (a spectroscopic method capable of exciting small molecules at a low-enough frequency to excite the large-amplitude motions of, here, short peptides).

I was given a momentary pause on the way to coffee this morning listening to Chick Corea’s Trilogy album when one of several of Brian Blade’s solos reminded me of what Art Taylor said of being a great drummer. “Know the songs.” There’s a similarity between drum solos and science graphics – you can either do whatever-the-hell you want as long as it looks/sounds great, or you can take the effort to make both reference strongly back to the theme. Hearing the melody in a drum solo and extracting the key points of an article from just one image are not at all dissimilar. In both cases, you get reinforcement (to either direction) from the ones paying the most attention.

With that digression aside – you may have asked yourself, “Just how did he manage those smooth, reflective, luscious springs in POV-Ray?“ My suspicion was that someone must have rendered a spring in POV-Ray in the last decade and provided the .pov file in some directory somewhere online. That search eventually produced fruit in the form of a wonderful set of tutorials by Friedrich A. Lohmueller. The good news was that his file provided all the obvious basics – take a rendered sphere and make it walk a spiraling path along an axis, leaving images of itself all the way down until N number of coils were generated. The texture, lighting, color scheme, etc., were all secondary. That said, his .pov file references back into a few files for colors(.inc), finish(.ini), and textures(.inc) that made the .pov a little less portable if you didn’t have a proper POV-Ray installed (and, being on a Mac, I’m still using MEGAPov until a miracle occurs and a new version of POV-Ray is released). These color/texture calls are just as easily embedded into the .pov file itself to make life easier. The result is the .pov file below, containing a reformed version of his original spring .pov file, some different labeling to point out where changes can occur, the call of colors by rgb, and blocked out “finish” sections so you can change the look of the spring to taste.

Download spring_somewhereville_dot_com.pov

// created by Friedrich A. Lohmueller, 2003 / 2010 / Jan-2011
// modified by Damian G. Allis, somewhereville.com, Mar-2016

// #include "textures.inc"

global_settings
	{
	assumed_gamma 1.0
	}

camera
	{
	angle 25                              //   smaller = closer
        location  < 0.0, 1.0, -5.0 >          //   -5.0 = distance to spring
        right x * image_width / image_height  //   want it larger --> go less neg.
        look_at < 0.0, 1.0, 0.0 >             //   want is smaller --> go more neg.
	}

light_source
	{
	< 1500, 2500, -2500 >
	color rgb < 1.0, 1.0, 1.0 >
	}

background 
	{
    color rgb < 1.0, 1.0, 1.0 >
	}

//
// begin the math to make the spring by spiraling a single sphere
//

#declare ampli = 0.50 ;                     // stretches and compresses the spring
#declare min_length = 0.80 ;
#declare mid_length = ampli + min_length ;
#declare time_test = 0.25 ;                 //0.25/0.75 shows max/min extention

#declare sprnglngth = mid_length + ampli * sin((clock + time_test) * 2 * pi) ;

#declare spiral =

union
	{
 	#local n_per_rev = 300 ;                   // spheres per spring revolution
 	#local n_of_rev = 4.00 ;                   // total coil count for the spring
 	#local h_per_ref = sprnglngth / n_of_rev ; // rise per revolution
 	#local nr = 0 ;                            // start loop
 	#while (nr < n_per_rev * n_of_rev)         // loop the spring sphere until...
    sphere
		{
    	< 0, -0.4, 0 > , 0.05                    // 0.05 adjusts the sphere diameter
    	translate< 0.25, -nr * h_per_ref / n_per_rev, 0.0 >
        rotate< 0, nr * 360 / n_per_rev, 0 >
		texture
			{
			pigment 
				{
				rgb < 0.658824, 0.658824, 0.658824 >
				}
            finish                               // adjust below to taste
        		{
            	ambient 0.050 
            	diffuse 0.500 
            	phong 0.1 
            	phong_size 2.500 
            	specular 0.500
		        reflection 0.15
		        brilliance 8
		        roughness 0.1
				}
			}
		}
	#local nr = nr + 1 ;
	#end
	} 

//
// end the math to make the spring by spiraling a single sphere
//

object
	{
	spiral translate< 0.0, 2.3, 0.0>       // translates "spiral" on the screen
	}

If you download the .pov file and run it, you should produce the spring image below – the fun is yours to make modifications to the file and see what those modifications do.

2016may13_spring

New B12-Insulin-TCII-Insulin Receptor Cover Image For This Month’s ChemMedChem (March 2009)

As was the case for the first ChemMedChem December, 2007 cover issue (posted previously), the cover story in this month’s issue is a communication by myself and members and collaborators of the Robert Doyle Group here at Syracuse University.  In this case, the work for the cover image actually went into computational research published in the associated article (instead of just a pretty cover image to complement the associated article, which was the intent of the previous cover).

The image below shows the Transcobalamin II (TCII) protein (in teal ribbons, with a bound cyanocobalamin (B12) shown in red.  The PDB code for this complex is 2BB5) sitting within the surface-accessible fragment of the gigantic insulin receptor (PDB code 2DTG.  The cell membrane would be at the bottom of this image, with the remainder of the complete protein sitting both within the cell membrane and then into the cytoplasm).  Saving the lead-up to this structure generation for the associated published article, this image was created to show one of the most important steps in the Oral Insulin project being worked on in the Doyle Group, with the fact that we know it works making the validity of the image content all the more relevant.  In brief, this figure shows that the TCII/B12-Insulin complex can fit within the insulin receptor such that the insulin molecule can bind to its receptor position on the appropriately described insulin receptor (IR), thereby instigating the cascade of events that leads to cellular glucose uptake.

For a larger view, click on the image.

Like many of the protein structures I render, this image would not have been possible without VMD and MegaPOV, my favorite OSX POV-Ray variant (there’s quite a bit of Photoshop layering as well).  The final layout for the cover is below, which I think would have benefited from the aerial view on the upper left side being shifted slightly to the left to fill out the black square.

According to the ChemMedChem website:

The cover picture shows three views of a vitamin B12-insulin conjugate bound to transcobalamin II, docked in the insulin receptor (IR). This study reveals how the structure of an orally deliverable insulin changes in solution after vitamin B12 conjugation and its effect on IR binding capacity. The results demonstrate that chemical modification of insulin by linking relatively large pendant groups does not interfere with IR recognition. For more details, see the Full Paper by T. J. Fairchild, R. P. Doyle, et al. on p. 421 ff.

To date, the associated work has received some additional linkage, both in the form of inclusion in the Spotlight list in Angew. Chem. Int. Ed. 2009, 48, 2072 – 2073 and, for those looking for a more pop-sci discussion of the applications of the research, New Scientist (Insulin Chewing Gum, 14 January 2009).  PDFs of the associated content are provided here for Angewandte Chemie and New Scientist.

There is a considerable amount of additional computational work being done on this system and the complete B12 pathway for potential use in various other applications.  Stay tuned for next year’s cover.

www3.interscience.wiley.com/journal/110485305/home
www3.interscience.wiley.com/journal/117354609/issue
www.somewhereville.com/?p=103
chemistry.syr.edu/faculty/doyle.html
www.syr.edu
en.wikipedia.org/wiki/Transcobalamin
en.wikipedia.org/wiki/Cyanocobalamin
www.rcsb.org/pdb/home/home.do
www.rcsb.org/pdb/explore/explore.do?structureId=2BB5
en.wikipedia.org/wiki/Insulin_receptor
www.rcsb.org/pdb/explore/explore.do?structureId=2DTG
en.wikipedia.org/wiki/Cytoplasm
en.wikipedia.org/wiki/Insulin
www.ks.uiuc.edu/Research/vmd
megapov.inetart.net
www.apple.com/macosx
www.povray.org
en.wikipedia.org/wiki/Adobe_Photoshop
www3.interscience.wiley.com/journal/122232189/issue
www.newscientist.com/article/dn16413-invention-insulin-chewing-gum.html