MERCURY CONFERENCE IN
July 30 - August 1, 2003
speakers gathered together for a group
photo after the conference talks.
Computation of Chemical and Physical Properties, National Institutes
of Standards and Technology, Computational Chemistry Group.
Jordan, Molecular & Materials Simulations, University
of Pittsburgh, Department of Chemistry. Abstract...
Merz, Applying Quantum Mechanics to Biological Systems
& Quantum Bioinformatics, Pennsylvania State University, Department
of Chemistry. Abstract...
Murray, Molecular Surface Electrostatic Potentials and Condensed
Phase Properties, University of New Orleans, Department of Chemistry.
Sahai, Aqueous and Surface Geochemistry, University
of Wisconsin, Madison, Department of Geology & Geophysics. Abstract...
Simmerling, Computational Structural Biology, State
University of New York at Stony Brook, Department of Chemistry.
York, Biomolecules in Solution, University of Minnesota,
Department of Chemistry. Abstract...
"Molecular and Materials Simulations"
Molecular clusters tend to have very complex potential energy surfaces,
making it difficult to locate the global minima and also to converge
finite temperature simulations. Extensions of the Monte Carlo procedure
to deal with these problems will be discussed. Results will be presented
for small water clusters as well as for conformationally flexible
biomolecules. A novel procedure for carrying out Monte Carlo simulations
using ab initio energies will also be considered.
(1) L.J. Munro,
A. Tharrington, and K.D. Jordan, "Global Optimizations and
Finite Temperature Simulations of Atomic and Molecular Clusters",
Computer Phys. Comm., 145, 1-23 (2002)
R. A. Christie and K. D. Jordan, "Finite Temperature Behavior
of H+(H2O)6 and H+(H2O)8",
J. Phys. Chem., 106, 8376-8381 (2002)
J.M. Pedulla, K. Kim and K.D. Jordan, "Theoretical Study of
the n-Body Interaction Energies of the Ring, Cage and Prism Forms
of (H2O)6", Chem. Phys. Lett., 291,
J.M. Pedulla and K.D. Jordan, "Melting Behavior of the (H2O)6
and (H2O)8 Clusters", Chem. Phys., 239,
C.J. Gruenloh, J.R. Carney, C.A. Arrington, T.S. Zwier, S.Y. Fredericks,
and K.D. Jordan, "Infrared Spectrum of a Molecular Ice Cube:
The S4 and D2d Water Octamers in Benzene-(Water)8",
Science 276, 1678-1681 (1997)
C. J. Tsai and K. D. Jordan, "Use of the Histogram and Jump
Walking Methods for Overcoming Slow Barrier Crossing Behavior in
Monte Carlo Simulations: Applications to the Phase Transitions in
the (Ar)13 and (H2O)8 Clusters", J. Chem.
Phys., 99, 6957-6970 (1993)
C. J. Tsai and K. D. Jordan, "Use of an Eigenmode Method to
Locate the Stationary Points on the Potential Energy Surfaces of
Selected Argon and Water Clusters", J. Phys. Chem., 97,
All-Electron Modeling of Biomolecular Systems: Applications to Drug
the explosion in the availability of high-resolution X-ray structures
of biomolecules there is an ever increasing need to annotate this
structural data in order to extract, for example, information regarding
the folding of these molecules as well as their interactions with
small-molecule therapeutics and their environment(s). In this presentation,
we will argue that quantum mechanics is now able to annotate available
biomolecular structures in unique ways. In order to support this
notion we will describe our recent efforts at applying semiempirical
linear-scaling methodologies to biological systems. First, we will
briefly discuss the divide and conquer approach (D&C) as applied
to semiempirical theory at the NDDO level (i.e., MNDO, AM1 and PM3).[1,2]
We will also demonstrate the performance of the method and discuss
its range of applicability to solve biologically and pharmaceutically
relevant problems. In order to begin to widely apply semiempirical
linear-scaling methodologies to biological systems solvent must
be included in the calculations. Thus, we will describe the implementation
and application of Poisson-Boltzmann (PB) methodologies that use
charge distributions determined using these quantum mechanical methodologies.
Next, we will describe the development of quantum mechanics based
protein/small molecule scoring functions that can be used to supplement
standard docking protocols and classical scoring procedures.
The final topic will cover the development of a Quantum Bioinformatics
Database (QBD) that is capable of storing and retrieving quantum
mechanically derived information (e.g., charge distributions, MOs,
total energies, etc.) regarding biomacromolecules and biologically
relevant small molecules and then analyzing the resulting data in
(1) Dixon, S.L. and K.M. Merz, Jr., Semiempirical Molecular Orbital
Calculations with Linear System Size Scaling. J. Chem. Phys., 1996.
104: p. 6643-6649.
(2) Dixon, S.L. and K.M. Merz, Jr., Fast, Accurate Semiempirical
Molecular Orbital Calculations for Macromolecules. J. Chem. Phys.,
1997. 107(3): p. 879-893.
(3) van der Vaart, A.; Suarez, D. and K. M. Merz, Jr. Critical Assessment
of the Performance of the Semiempirical Divide and Conquer Method
for Single Point Calculations and Geometry Optimizations of Large
Chemical Systems J. Chem. Phys. 2000, 113(23):
(4) Gogonea, V. and K.M. Merz Jr., Fully Quantum Mechanical Description
of Proteins in Solution. Combining Linear Scaling Quantum Mechanical
Methodologies with the Poisson-Boltzman Equation. J. Phys. Chem.
A, 1999. 103(26): p. 5171-5188.
"An Adventure into the World of Chemistry: Molecular Electrostatic
Potentials and Molecular Properties"
Any distribution of charge creates an electrical potential in the
surrounding space, as dictated by Coulomb's law. When this distribution
of charge is the nuclei and electrons of an atom or molecule "frozen
in space," the resulting electrical potential is called the
"electrostatic" potential. The electrostatic potential
is a fundamental determinant of intrinsic atomic and molecular properties
(e.g. energies, chemical potentials, covalent radii) as well as
a well-established guide to chemical reactive behavior, especially
in noncovalent interactions. In my talk, I will focus upon the use
of the molecular electrostatic potential as a tool in the elucidation
of molecular interactions, both in qualitative and quantitative
applications. My intention is to introduce a realistic way of looking
at molecules which transcends atomic and bond symbols and which
provides a window into their world.
(1) T. Brinck, J. S. Murray and P. Politzer, Mol Phys, 76,
(2) J. S. Murray, T. Brinck, P. Lane, K. Paulsen and P. Politzer,
J Mol Struct (Theochem), 307, 55 (1994).
(3) H. Hagelin, T. Brinck, M. Berthelot, J. S. Murray and P. Politzer,
Can J Chem, 73, 483 (1995).
(4) J. S. Murray and P. Politzer, J Mol Struct (Theochem), 425,
(5) P. Politzer, J. S. Murray and Z. Peralta-Inga, Int J Quantum
Chem, 85, 676 (2001).
Computational Chemistry to Study Biomineralization"
Biominerals are composite materials produced by organisms via
the interaction of organic compounds with dissolved inorganic species.
The composite nature renders unique materials properties such as
high fracture toughness and mesoporosity, inspiring scientists to
attempt biomimetic materials synthesis. Controlled design and production
of biomaterials requires an understanding of the reaction pathways
that lead to the nucleation of the earliest crystals. The angstrom
to nanometer size range of the earliest solid phases formed makes
their identification and characterization by traditional methods
a difficult task. We have, therefore, developed a novel approach
combining quantum chemical computational method with vibrational
and NMR spectroscopy to identify the species involved in the reaction
pathways for biogenic silica (amorphous SiO2) precipitation
by eukaryotic microorganisms such as diatoms and sponges and, for
precipitation on the surfaces of orthopedic bioceramic implants
we have used Hartree-Fock theory to calculate optimized structures,
formation energies, and 29Si NMR chemical isotropic shifts
of organosilicates putatively involved in diatom metabolism. When
compared with experimental spectra, we show that it is energetically
possible to use quadra-coordinated organosilicates for storing silicon
intracellularly, thus increasing silicon solubility until required
for silica precipitation. Further, we find that penta- and hexa-coordinated
organosilicates are unlikely to be stable under natural biological
is experimentally observed that silica ceramic surfaces promote
the growth of calcium phosphate from aqueous solutions simulating
body fluids. We have used Hartree-Fock theory to identify the active
surface site on the bioceramic surfaces and identified the most
likely reaction mechanism by comparing calculated vibrational frequencies
to experimental Raman and FTIR spectra, and calculated 29Si
and 31P NMR shifts with experimental spectra.
"Simulations of Protein Structure and Folding: What Can We
One of the most important challenges for computational biophysics
is the prediction of accurate atomic-detail models of protein structure
when experimental data is unavailable. This seminar will present
our recent work toward this goal, including the first successful
blind prediction of structure for a mini-protein. However, simulations
have the potential to provide much more than native conformations;
it may be possible to determine why that particular structure is
preferred, and what physical interactions stabilize it. We therefore
investigated a variety of sequence mutants of the mini-protein,
and simulation results will be compared to experimental data.
Finally, simulations have the potential to provide new insight into
the folding process itself. Equilibrium and non-equilibrium simulations
for several model sequences will be compared to determine if a consistent
view of the folding landscape can be obtained from each type of
calculation, and to evaluate the reliability of these methods.
Structure Predicition and Folding Simulations of a Stable Protein
generation quantum models for biological systems in solution"
computational chemistry is faced with exciting new challenges in
the new millennium. A rapidly advancing research area is at the
interface of traditional disciplines in chemistry and biology, and
involves the integration of experimental and theoretical methods
that, together, are able to paint a detailed picture of processes
that span individual molecule, nano-scale and even meso-scale domains.
Consequently, it is a major goal of computational chemistry to develop
"multi-scale" quantum models that are able to simultaneously
span a broad range of spatial and temporal domains.
this talk, several advancements in the development of accurate quantum
models for molecular simulations of biological reactions and the
characterization of macromolecular reactivity are presented. Techniques
that will be discussed include: new quantum models for hybrid quantum
mechanical/molecular mechanical activated dynamics simulations,
and so-called linear-scaling electronic structure and solvation
methods for macromolecules. Applications will focus on the study
of phosphate hydrolysis reactions in solution and catalyzed by ribozymes,
and the determination of chemical reactivity indices of important
drug targets such as the HIV nucleocapsid