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Computational Modeling and Visualization of Biomolecules. Preston J. MacDougall Middle Tennessee State University With contributions by: Dr. Christopher E. Henze, NASA Ames Research Center Profs. Tibor Koritsanszky and Anatoliy Volkov, MTSU
Preston J. MacDougall
Middle Tennessee State University
With contributions by:
Dr. Christopher E. Henze, NASA Ames Research Center
Profs. Tibor Koritsanszky and Anatoliy Volkov, MTSU
Drs. Michal Chodkiewicz, Hui Yang, and Yevgeni Moskovitz, MTSU
Funding of personnel, a dedicated cluster, and
the 4x4 3D-Hyperwall at MTSU, provided by
the Office of Science in the U.S. Department
of Energy; grant #DE-SC00005094
The new Ph.D. in Computational Science has
provided a home for the MTSU 3D-Hyperwall
CGI fly-through of New Science Building: http://mtsunews.com/sciencebuilding/#!
Science should lead technology, however.One should first ask “How will molecules be modeled?” and “What properties of that model will be most instructive when visualized?”
often take short-cuts to the density
> r(r) <
reduction: integration over
all but 3 spatial dimensions
and loss of phase information
synthesis: by Fourier series
from zero dimensional X-ray
*These short-cuts are like scaffolds.
They are only a means to an end.
density, either from theory or experiment,
you will find that it is rather pedestrian in
appearance. What then?
> r(r) <
subtracting reference densities
partitioning the density
differentiating the total density
(let’s consider option no. 3)
> r(r) <
* For a broad overview, consult “A Matter of Density”, ed. N. Sukumar (Wiley, 2013)
Even simple molecules like CO can have controversial (point) “charge distributions”. Which end is negative? By considering the total electron density, concepts such as atomic charge, bond paths and molecular structure, can be defined with reference to (r) (R. F. W. Bader, “Atoms in Molecules – A Quantum Theory” (Oxford Univ. Press, 1990))
depressions and necks are + , humps and shoulders are -
Energetically, it appears in the local
(1/4)2(r) = 2G(r) + V(r)
2(r) = ¶2(r)/¶x2 + ¶2(r)/¶y2 + ¶2(r)/¶z2
R. F. W. Bader (1931 - 2012)
Chemical Eye on a Theoretical Truck
In Maxwell’s interpretation of the
Laplacian of any scalar function,
negative regions are “local concentrations”
and positive regions are “local depletions.”
(r) - ave. = -(1/10)r22(r) + O4
where ave.is the mean value of
within a small sphere of radius r
centered at r.
James Clerk Maxwell (1831 – 1879)
The pattern of local concentrations and depletions in a water molecule reveals that the “charge cloud” does indeed have a “shell structure” and that the valence shell charge concentration (VSCC) has a sub-shell structure that can be mapped onto the Lewis structure of the molecule
(3,+3) CP in the vicinity of Oxygen
(3,-3) CP in the vicinity of Hydrogen
For highly symmetrical molecules, such as Cr(CO)6, Fe(CO)5, and Ni(CO)4, 2D contour plots may suffice(MacDougall and Hall, Trans. Am. Cryst. Assoc., 26, 105 (1990))
Algorithms “boosted” by NASA rocket scientists can visualize the entire VSCC (here, of oxygen in water). It is a “separation surface” in fluid dynamics terminology(MacDougall and Henze, Theor. Chem. Acc. (2001))
EVolVis – an interactive volume visualization tool that lets one “scan” and “focus” on multiple topological features in the Laplacian of the total electron density of molecules (either measured or computed)
This visualization tool conveys key concepts of bonding and reactivity in a manner that is in perfect concert with an intriguing statement by a pioneer in theoretical chemistry
“It is always of interest to find that some of our most modern scientific ideas have been vaguely anticipated by scientists of earlier centuries. One of the ideas of Lemery, a contemporary of Robert Boyle, is amusingly discussed in a well known history of chemistry, as follows: ‘Yet one of his theoretical conceptions was very odd, and shows how far astray a capable man may wonder, when he deserts observed facts for philosophical speculations. He thought that chemical combination between two substances, such as an acid and a base, might be accounted for by supposing that the particles of one were sharp, and those of the other porous, and that chemical combination was effected by the fitting of the points into the holes!’”
G. N. Lewis (1934)
Pseudo-molecules(These can be rapidly constructed from a pseudoatomic library of highly transferable “atoms”. Here, the total charge density of the 11-mer polypeptide cyclosporin A is modeled.)
(Koritsanszky, Volkov and Chodkiewicz, “New Directions in Pseudoatom-Based X-ray Charge Density Analysis” in “Structure and Bonding” (2011))
Structure Bank (~1300)
Parallel molecules on the NASA Ames Hyperwall(Sandstrom, Henze and Levit, Proc. of Coordinated & Multiple Viewsin Exploratory Visualization (I.E.E.E., 2003))
Pharmacophores are typically modeled by featureless “features”, color-coded for H-bond donors, H-bond acceptors, ionizing groups, hydrophobic groups etc…
(MacDougall and Henze, in “The Quantum Theory of Atoms in Molecules:From Solid State to DNA and Drug Design” Matta & Boyd (Wiley-VCH, 2007))
Next steps: Examine the docking of drug candidates to the ATP-binding site of E. coli DNA gyrase – a promising target in multi-drug resistant bacteria.
A Chemical Eye on Aesthetics
MURFREESBORO, TN (2004-11-12) MTSU
Chemistry Professor Dr. Preston MacDougall ponders the relationship between Art and Chemistry.
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Thanks for listening!