July 30 - August 1, 2003

Keynote speakers gathered together for a group
photo after the conference talks.

List of Speakers
Speaker Abstracts


List of Speakers

Anne Chaka, Computation of Chemical and Physical Properties, National Institutes of Standards and Technology, Computational Chemistry Group.

Ken Jordan, Molecular & Materials Simulations, University of Pittsburgh, Department of Chemistry. Abstract...

Kennie Merz, Applying Quantum Mechanics to Biological Systems & Quantum Bioinformatics, Pennsylvania State University, Department of Chemistry. Abstract...

Jane Murray, Molecular Surface Electrostatic Potentials and Condensed Phase Properties, University of New Orleans, Department of Chemistry. Abstract...

Nita Sahai, Aqueous and Surface Geochemistry, University of Wisconsin, Madison, Department of Geology & Geophysics. Abstract...

Carlos Simmerling, Computational Structural Biology, State University of New York at Stony Brook, Department of Chemistry. Abstract...

Darrin York, Biomolecules in Solution, University of Minnesota, Department of Chemistry. Abstract...



Speaker Abstracts

"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)

(2) 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)

(3) 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, 78-84 (1998)

(4) J.M. Pedulla and K.D. Jordan, "Melting Behavior of the (H2O)6 and (H2O)8 Clusters", Chem. Phys., 239, 593-601 (1998)

(5) 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)

(6) 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)

(7) 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, 11227-11237 (1993)


"Towards All-Electron Modeling of Biomolecular Systems: Applications to Drug Discovery"

With 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.[3] 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.[4] 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.[4] 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 meaningful ways.

(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): p. 10512-10523.
(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, 609 (1992).
(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, 107 (1998).
(5) P. Politzer, J. S. Murray and Z. Peralta-Inga, Int J Quantum Chem, 85, 676 (2001).


"Using 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 hydroxyapatite (Ca5(PO4)3(OH)) precipitation on the surfaces of orthopedic bioceramic implants in vertebrates.

Specifically, 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 conditions.

It 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 Learn?"

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.

All-Atom Structure Predicition and Folding Simulations of a Stable Protein


"New generation quantum models for biological systems in solution"

Modern 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.

In 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



Hamilton College
Clinton, NY


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