ChemNews.Com VOL 6 NO 4
Computer Power Makes for Better Modeling
Jerald J. Baronofsky
As desktop computers become faster (now up to 450 MHz) and
possess larger and larger memory capabilities (>128 MB RAM) their
performance can approach the computational levels that workstations
and minicomputers were at only a few years ago. The cost of storage
memory has dropped dramatically in the past year as well, not to mention
availability of "floating" 1 GB storage containers in the form of
Jaz drive diskettes. What this means is anyone today can perform computational
chemistry calculations that five years ago were strictly limited to
dedicated computational chemists. It allows ab initio calculations
to be performed routinely on molecules more complex than water using
the latest model PCs and Macintoshes. It enables users to perform
MOPAC (i.e. semi-empirical) calculations on sizable structures to
visualize orbitals, electrostatic potentials, charge densities and
other informative surface maps. Thus, for those chemists and biochemists
willing to take the time to learn how to use the excellent modeling
and analysis programs available, there is a huge opportunity for them
to become their own computational chemist!
Despite these great opportunities I've noticed an interesting phenomenon
in the computer world which reminds me of the Law of Entropy. Entropy
poses that molecules will disperse into a vacuum so as distribute
themselves equally throughout its volume, if there are no opposing
forces and will, in essence occupy, all available space. The parallel
computer phenomenon is that despite larger memory capacities and
faster computer speed, the space requirements for newly developed
software expands so as to fully occupy what is available on your
latest hard drive. One has only to look at the size of memory needed
to install Windows 98 and Microsoft Office 98 compared to the requirements
of the earlier versions of those programs six or seven years ago.
In the world of desktop modeling, programs are following the same
trend by offering more features, faster computations and better
graphical displays. The demands on RAM capacity and hard drive space
have increased dramatically. The payoff, in much more productive
programs, is immense. And no self-respecting modeling program would
be without several add-on programs which provide specific computational
features (such as QSAR analysis or conformational searching) absent
from the base program. These add-ons may be by a third party or
produced by the model developer.
|
| There is a huge
opportunity for chemists & biochemists to become their own
computational chemist! |
|
But, as programs offer more features and become more complex, a
void created for simpler, more basic, modeling packages is being
filled by junior versions of the more sophisticated ones. CambridgeSoft,
like many other software developers, offers student versions of
their programs which just provide basic modeling functions at an
entry-level.
Chem3D
The Chem3D modeling program can certainly take advantage of the advances
in desktop computers. Modeling programs are always subject to limitations
on the RAM and speed of the microprocessor. The molecular mechanics,
semi-empirical calculations and 3D surface visualization are facilitated
greatly by the computer's progress. With Chem3D's integration with
ChemDraw and ChemFinder, this makes a powerful program even better.
Gaussian
Gaussian 98 is one of the programs to benefit most from the greater
power available on the desktop. Only a short while ago users were
restricted to UNIX workstations. With the new release, however, desktop
conformational chemists have a powerful ab initio package with many
new features, such as: 1. ONIOM calculations to allow analysis on
large systems through layering of accuracy around the site of interest,
2. Excited state modeling with ZINDO, 3. time-dependent and DFT methods,
4. predictions of Raman intensities, NMR shielding tensors and vibrational
circular dichroism, and 5. distinguishing between solution and gas
phase modeling. The Chem3D Gaussian interface allows visualization
of the structures after running the Gaussian job.
MOPAC 97
Also benefiting from the expansion of memory is MOPAC 97. Semi-empirical
calculation run times have diminished greatly and the size and complexity
of molecules to be addressed expanded. The last release of MOPAC introduced
d-orbital calculations, which added a whole new level of complexity
that would have been impossible only a few short years ago. Also achievable
now are transition and excited state properties. Dr. James Stewart,
MOPAC developer for Fujitsu says, "Chem3D was the first modeling program
to provide a fully functional MOPAC 97 for the desktop. I use it frequently."
Conformer
Dr. David Wertz, President of Princeton Simulation writes, "Today's
desktop computers are so powerful that computationally intensive calculations,
like conformational searching can be done on them. One no longer needs
a high end workstation. This makes routine use of conformational searching
not only cost effective but convenient and easy to do." During a conformational
search the number of potential starting molecular conformations expands
geometrically for each rotatable bond added to the analysis. Conformer,
which was developed exclusively for Chem3D, provides a powerful tool
to not only identifiy all stable conformations, but to analyze the
distribution of the conformations and compare/explain bioactivity
differences among molecules with similar structures.
SciLogP and SciQSAR
SciLogP and SciQSAR are distinct from other programs providing similar
analysis by utilizing three dimensional information about the molecules
to create property prediction algorithms. For small organic molecules
this is not particularly significant because most property prediction
programs can handle simple stuff very easily. However, as one begins
to look at larger, highly substituted compounds which may have internal
conformational factors (e.g. internal H-bonds, strong dipole moment,
etc.) that affect their properties, simple fragment-based methods
will not produce accurate estimates. SciLogP and SciQSAR analyses
can be made as accurate as the data from the training set of molecules
you provide to create a focused prediction algorithm. Both programs
are available in Chem3D file format versions.
gNMR
gNMR from Cherwell Scientific is an NMR prediction program for both
Windows and Macintosh machines. The program can import molecular files
from several drawing and modeling programs and simulate an NMR spectrum
for the imported structures. Links are created between the spectrum
and the structure to allow identification of spectral peaks with the
corresponding atoms. The latest release boasts faster display capabilities,
enhanced user interface for graphical display of spectra and new approximation
and calculation formulas.
Adam Hodgkin, managing director of Cherwell Scientific said, "NMR
calculations can be very demanding of processor power. The computational
limit which matters is the number of atoms or spin systems that
can be addressed. It is now feasible to produce a simulation package
on the desktop which will handle up to 50 spin systems."
Conclusions
Computational chemistry software developers have much to be thankful
for. Many constraints on the complexity and size of the programs under
development from the past have become moot. RAM is so inexpensive
now it is not unreasonable to require the user to have 64 MB RAM for
a good computational package to perform many of the calculations featured.
The newest PC models operating at 450 MHz are only a prelude to more
powerful machines to come. Finally, 10+ GB hard drives for under $500
provide enough storage space to last ardent computational chemists.
|
Program
Developer |
Software
Compatibility |
Calculation
Method |
Program
Overview |
Suggested
Expertise |
System |
|
Chem3D
CambridgeSoft
www.camsoft.com |
ChemDraw,
ChemOffice |
Semi-Empirical
& Molecular Mechanics |
General Desktop Modeling
|
All Levels |
Win
Mac |
|
MOPAC
Fujitsu Ltd.
www.fujitsu.com |
Chem3D |
Semi-Empirical |
Calculation of molecular
& electronic properties |
Inter-
mediate |
Win
Mac |
|
Gaussian
Gaussian Inc.
www.gaussian.com |
Chem3D |
Ab initio &
Semi-Empirical |
Calculation of molecular
& electronic properties |
Expert |
Win
Mac
UNIX |
|
Conformer
Princeton Simulations
www.conformer.com |
Chem3D |
Molecular
Mechanics |
Conformational
analysis |
Novice |
Win
Mac |
|
gNMR
Cherwell Scientific Ltd.
www.cherwell.com |
Chem3D,
ChemDraw |
NMR Theory (Pople) |
Simulation of
NMR information |
Novice |
Win
Mac |
|
SciVision
SciLogP & SciQSAR
www.scivision.com |
Chem3D |
Molecular Mechanics |
3D Property Prediction |
Inter-
mediate |
Win |
|
