Biomedical subjects

Peter J Ortoleva

Publications and source records attributed to Peter J Ortoleva.

8 recordsLinked to original sources

PubMed2006

Viral structural transitions: an all-atom multiscale theory.

An all-atom theory of viral structural transitions (STs) is developed based on a multiscale analysis of the N-atom Liouville equation. The approach yields an understanding of viral STs from first principles and a calibrated interatomic force field. To carry out the multiscale analysis, we introduce slow variables characterizing the whole-virus dynamics. Use of the "nanocanonical ensemble" technique and the fundamental hypothesis of statistical mechanics (i.e., the equivalence of long-time and ensemble averages) is shown to imply a Fokker-Planck equation yielding the coarse-grained evolution of the slow variables. As viral STs occur on long time scales, transition state theory is used to estimate the energy barrier of transition between free energy wells implied by observed hysteresis in viral STs. Its application to Nudaurelia capensis omega virus provides an upper bound on the free energy barrier when a single dilatational order parameter is used. The long time scale of viral STs is shown to follow from the aggregate effect of inertia, energy barrier, and entropic effects. Our formulation can be generalized for multiple order parameter models to account for lower free energy barrier pathways for transition. The theory with its all-atom description can be applied to nonviral nanoparticles as well.

Computer Simulation↗

PubMed2006

Involatile nanodroplets: an asymptotic analysis.

The structure of nanometer-scale droplets of weakly volatile liquids arises through the interplay of strong intermolecular attraction, and core intermolecular repulsion, interfacial forces, and the large, negative chemical potential of the low density vapor with which it is in equilibrium. Using a van der Waals equation of state and a mesoscopic multiphase model, the structure of such nanodroplets is determined via an asymptotic analysis in terms of the ambient to critical temperature ratio. The structure of a spherical droplet is obtained as the solution of a simple "shooting" problem. The intradroplet pressure profile and a minimal droplet size are determined. The high pressure in the core of the droplet gives evidence for the preferred melting there for systems like water with a negative volume of melting. Our methodology can be generalized to multiphase droplets, as well as to composite structures wherein viruses or other nanoparticles are embedded.

Journal Article↗

PubMed2005

Nanoparticle dynamics: a multiscale analysis of the Liouville equation.

A theory of nanoparticle dynamics based on scaling arguments and the Liouville equation is presented. We start with a delineation of the scales characterizing the behavior of the nanoparticle/host fluid system. Asymptotic expansions, multiple time and space scale techniques, the resulting coarse-grained dynamics of the probability densities of the Fokker-Planck-Chandrasekhar (FPC) type for the nanoparticle(s), and the hydrodynamic models of the host medium are obtained. Collections of nanoparticles are considered so that problems such as viral self-assembly and the transition from a particle suspension to a solid porous matrix can be addressed via a deductive approach that starts with the Liouville equation and a calibrated atomic force field, and yields a generalized FPC equation. Extensions allowing for the investigation of the rotation and deformation of the nanoparticles are considered in the context of the space-warping formalism. Thermodynamic forces and dissipative effects are accounted for. The notion of configuration-dependent drag coefficients and their implications for coagulation and consolidation are shown to be natural consequences of the analysis. All results are obtained via formal asymptotic expansions in mass, size, and other physical and kinetic parameter ratios.

Models, Theoretical↗

PubMed2004

Simulated complex dynamics of glycolysis in the protozoan parasite Trypanosoma brucei.

Glycolysis in Trypanosoma brucei was modeled using a reaction transport simulator and tested for possible complex dynamics. The glycolytic model is multi-compartmentalized and accounts for the exchange of metabolites between the glycosomes, cytosol, mitochondrion and the host medium. The model is used to examine the effects of a range of culture medium concentrations of oxygen on the glycolysis of T. brucei. Our results are in good agreement with steady-state experiments. We also find that under aerobic conditions, increasing the activity of glycerol-3-phosphate dehydrogenase induces complex dynamics in the system. We report the presence of three distinct types of these dynamics. Varying the oxygen concentration in the medium can induce the transition between these dynamics.

Aerobiosis↗

PubMed2004

Classical density functional theory of orientational order at interfaces: application to water.

A classical density functional formalism has been developed to predict the position-orientation number density of structured fluids. It is applied to the liquid-vapor interface of pure water, where it consists of a classical term, a gradient correction, and an anisotropic term that yields order through density gradients. The model is calibrated to predict that water molecules have their dipole moments almost parallel to a planar interface, while the molecular plane is parallel to it on the liquid side and perpendicular to it on the vapor side. For a planar interface, the surface tension obtained is twice its experimental value, while the surface potential is in qualitative agreement with that calculated by others. The model is also used to predict the orientation of water molecules near the surface of droplets, as well as the dependence of equilibrium vapor pressure around them on their size.

Journal Article↗

PubMed2004

Efficient solution technique for solving the Poisson-Boltzmann equation.

The Poisson-Boltzmann (PB) equation has been extensively used to analyze the energetics and structure of proteins and other significant biomolecules immersed in electrolyte media. A new highly efficient approach for solving PB-type equations that allows for the modeling of many-atoms structures such as encountered in cell biology, virology, and nanotechnology is presented. We accomplish these efficiencies by reformulating the elliptic PB equation as the long-time solution of an advection-diffusion equation. An efficient modified, memory optimized, alternating direction implicit scheme is used to integrate the reformulated PB equation. Our approach is demonstrated on protein composites (a polio virus capsid protomer and a pentamer). The approach has great potential for the analysis of supramillion atoms immersed in a host electrolyte.

Algorithms↗

PubMed2003

Simulating cellular dynamics through a coupled transcription, translation, metabolic model.

In order to predict cell behavior in response to changes in its surroundings or to modifications of its genetic code, the dynamics of a cell are modeled using equations of metabolism, transport, transcription and translation implemented in the Karyote software. Our methodology accounts for the organelles of eukaryotes and the specialized zones in prokaryotes by dividing the volume of the cell into discrete compartments. Each compartment exchanges mass with others either through membrane transport or with a time delay effect associated with molecular migration. Metabolic and macromolecular reactions take place in user-specified compartments. Coupling among processes are accounted for and multiple scale techniques allow for the computation of processes that occur on a wide range of time scales. Our model is implemented to simulate the evolution of concentrations for a user-specifiable set of molecules and reactions that participate in cellular activity. The underlying equations integrate metabolic, transcription and translation reaction networks and provide a framework for simulating whole cells given a user-specified set of reactions. A rate equation formulation is used to simulate transcription from an input DNA sequence while the resulting mRNA is used via ribosome-mediated polymerization kinetics to accomplish translation. Feedback associated with the creation of species necessary for metabolism by the mRNA and protein synthesis modifies the rates of production of factors (e.g. nucleotides and amino acids) that affect the dynamics of transcription and translation. The concentrations of predicted proteins are compared with time series or steady state experiments. The expression and sequence of the predicted proteins are compared with experimental data via the construction of synthetic tryptic digests and associated mass spectra. We present the mathematical model showing the coupling of transcription, translation and metabolism in Karyote and illustrate some of its unique characteristics.

Cell Physiological Phenomena↗

PubMed2002

New space warping method for the simulation of large-scale macromolecular conformational changes.

A space warping method, facilitating the modeling of large-scale conformational changes in mesoscopic systems, is presented. The method uses a set of "global (or collective) coordinates" that capture overall behavior, in conjunction with the set of atomic coordinates. Application of the space warping method to energy minimization is discussed. Several simulations where the method is used to determine the energy minimizing structures of simple central force systems are analyzed. Comparing the results and behavior of the space warping method to simulations involving atomic coordinates only, it is found that the space warping method scales better with system size and also finds lower minima when the potential energy surface has multiple minima. It is shown that the transformation of [Ala16]+ in vacuo from linear to globular is captured efficiently using the space warping method.

Biopolymers↗