Peter J. Ortoleva

Background:

• Research Associate, Massachusetts Institute of Technology, 1970-75
• Alfred P. Sloan Research Fellow, 1980-82
• NATO Fellow, 1982
• Guggenheim Fellow, 1990.

The Center for Cell and Virus Theory is a research institute, the main objective of which is to develop mathematical and computational models of the physical and chemical processes underlying cell and virus behavior. We are addressing the challenge of understanding the workings of life on multi-, single- and sub-cellular scales. The interdisciplinary approach of the Center integrates methods from statistical mechanics, quantum chemistry, chemical kinetics, cell physiology, virology, biochemistry and computational sciences. Information theory is used to integrate models with data to arrive at a revolutionary automated model development, calibration and risk assessment approach. For more information please visit our website at biodynamics.indiana.edu.

Karyote®: a genomic, proteomic, metabolic cell simulator

A quantitative model of the behavior of a cell and its response to chemical disturbances in the extra-cellular medium, gene deletion/mutation, and the presence of other cells, is being developed at the Center. This model, Karyote, is based on the numerical solution of a set of reaction, transport and mechanical equations underlying cell dynamics. The behavior predicted by Karyote reflects the nonlinear dynamics of the cell reaction-transport system. Karyote is integrated with genomic, proteomic, metabolic and other experimental data through our novel information theory approach. The result is a novel automated procedure for tailoring Karyote to a given cell type; all predictions are accompanied by an assessment of risk and uncertainty. Karyote also serves as a prototype for a data archive with self-consistent automated interpretation of the rapidly expanding microarry, mass spectral and NMR databases. Karyote has great potential for accelerating drug discovery, optimizing treatment regimes, testing concepts in cloning and designing microbes for biotechnical and environmental remediation activities.

CellX^â: a multi-dimensional simulator

We are developing a simulator (CellX) that will yield the spatio-temporal dynamics of a cell, capturing the evolving gradients of molecular species within each of its compartments. The solution approach we have developed for CellX is based on a projection technique implied by the separation of temporal scales induced by the existence of slow vs. fast diffusing species as well as slow vs. fast reactions. The distinction between bulk species and those adsorbed at membranes or fibrils is accounted for by solving reaction-transport equations in 1- or 2- dimensions. This multiple spatial dimensional character of CellX allows it to capture the complexity of intra-cellular structure. An example for a simulation of E. coli is seen in Fig. 1, where color indicates variation in protein concentration at the inner-surface of the cell membrane and within its interior. The result for E. coli is an oscillatory wave of protein distribution.

VirusX ®: a multi-level virus simulator

A quantitative model of the structure and dynamics of a virus is being developed for fundamental and health sciences research. All-atom simulations have played an important role in molecular research. The large number of atoms in a virus and its immediate surroundings render these approaches unfeasible. We have developed and implemented a variety of advanced molecular modeling techniques that simultaneously account for atomic-scale processes and overall conformational changes to simulate these many-atom systems (Fig. 2). VirusX is being used to study the assembly and stability of partial and whole viruses. We also integrate this type of detailed model with our field theory of the host medium in which the virus resides.

Selected Publications:

"Role of attachment kinetic feedback in the oscillatory zoning of crystals grown from melts." In Self-Organization in Geological Systems: Proceedings of a Workshop Held 26-30 June 1988, University of California, Santa Barbara. P. Ortoleva, B. Hallet, A. McBirney, I. Meshri, R. Reeder, and P. Williams, eds. Earth Sci. Rev., 29, 183 (1990).

"Self-organization in geological systems: proceedings of a workshop held 26-30 June 1988, University of California, Santa Barbara," P. Ortoleva, ed. (B. Hallet, A. McBirney, I. Meshri, R. Reeder, and P. Williams, assoc. eds.). Earth Science Rev., 29, special issue (1990).

Nonlinear Chemical Waves. Chichester: John Wiley and Sons, 1992, 302 pp.

"Self-organization and nonlinear dynamics in sedimentary basins." Philos. Trans. R. Soc. London, Ser. A, 344, 171 (1993).

"Nonlinear dynamical aspects of deep basin hydrology: fluid compartment formation and episodic fluid release," with T. Dewers. Am. J. Sci., 294, 713 (1994).

Geochemical Self-Organization. Oxford University Press, 1994, 411 pp.

"Basin compartments and seals." In AAPG Memoir, vol. 61, P. Ortoleva, ed. Tulsa: American Association of Petroleum Geology, 1994, 477 pp.

"Genesis and dynamics of basin compartments and seals," with A. Al-Shaieb and J. Puckette. Am. J. Sci., 295, 345 (1995).

"Water films at grain-grain contacts: Debye-Huckel, osmotic model of stress, salinity, and mineralogy dependence," with F. Renard. Geochim. Cosmochim. Acta, 61, 1963 (1997).

"A geochemical reaction-transport simulator for matrix acidizing analysis and design," with X. Liu, A. Ormond, K. Bartko, and Y. Li. J. Pet. Sci. Eng., 17, 181 (1997).

"Glass transitions: a chemical kinetic/Landau theory." J. Phys. Chem. B, 101, 8324 (1997).

"Pressure solution in sandstones: influence of clays and dependence on temperature and stress," with F. Renard and J. P. Gratier. Tectonophysics, 280, 257 (1997).

"Self-organization during reactive fluid flow in a porous medium," with F. Renard, J. P. Gratier, E. Brosse, and B. Bazin. Geophy. Res. Lett., 25, 385 (1998).

"New space warping method for the simulation of large-scale macromolecular conformational changes," with K. Jaqaman. J. Comp. Chem., 23, 484 (2002).