Biomedical subjects

M W Deem

Publications and source records attributed to M W Deem.

7 recordsLinked to original sources

PubMed2006

Quasispecies theory for multiple-peak fitness landscapes.

We use a path integral representation to solve the Eigen and Crow-Kimura molecular evolution models for the case of multiple fitness peaks with arbitrary fitness and degradation functions. In the general case, we find that the solution to these molecular evolution models can be written as the optimum of a fitness function, with constraints enforced by Lagrange multipliers and with a term accounting for the entropy of the spreading population in sequence space. The results for the Eigen model are applied to consider virus or cancer proliferation under the control of drugs or the immune system.

Biological Evolution↗

PubMed2001

Dispersion coefficients from a field-theoretic renormalization of fluid mechanics.

We consider subtle correlations in the scattering of fluid by randomly placed obstacles, which have been suggested to lead to a diverging dispersion coefficient at long times for high Péclet numbers, in contrast to finite mean-field predictions. We develop a new master equation description of the fluid mechanics that incorporates the physically relevant fluctuations, and we treat those fluctuations by a renormalization group procedure. We find a finite dispersion coefficient at low volume fraction of disorder and high Péclet numbers.

Journal Article↗

PubMed2000

Differential transport of DNA by a rectified Brownian motion device.

An interdigitated electrode array (IDEA) device has been designed and used to transport DNA based on a Brownian ratchet mechanism. This migration is produced by the periodic formation of an asymmetric sawtooth electric field in the device. Oligonucleotides of 25, 50, and 100 bases in length were tested using two different array geometries. DNA transport as a function of DNA size, electric field frequency, and array geometry is shown to be in qualitative agreement with theory. Such a device could provide for DNA separations over a broad size range, and can be readily scaled as a component in a microfabricated DNA analysis system.

Animals↗

PubMed2000

Library design in combinatorial chemistry by Monte Carlo methods.

Strategies for searching the space of variables in combinatorial chemistry experiments are presented, and a random energy model of combinatorial chemistry experiments is introduced. The search strategies, derived by analogy with the computer modeling technique of Monte Carlo, effectively search the variable space even in combinatorial chemistry experiments of only modest size. Efficient implementations of the library design and redesign strategies are feasible with current experimental capabilities.

Combinatorial Chemistry Techniques↗

PubMed1999

DNA transport by a micromachined Brownian ratchet device.

We have micromachined a silicon-chip device that transports DNA with a Brownian ratchet that rectifies the Brownian motion of microscopic particles. Transport properties for a DNA 50-mer agree with theoretical predictions, and the DNA diffusion constant agrees with previous experiments. This type of micromachine could provide a generic pump or separation component for DNA or other charged species as part of a microscale lab-on-a-chip. A device with reduced feature size could produce a size-based separation of DNA molecules, with applications including the detection of single-nucleotide polymorphisms.

DNA↗

PubMed1999

A hierarchical approach to protein molecular evolution.

Biological diversity has evolved despite the essentially infinite complexity of protein sequence space. We present a hierarchical approach to the efficient searching of this space and quantify the evolutionary potential of our approach with Monte Carlo simulations. These simulations demonstrate that nonhomologous juxtaposition of encoded structure is the rate-limiting step in the production of new tertiary protein folds. Nonhomologous "swapping" of low-energy secondary structures increased the binding constant of a simulated protein by approximately 10(7) relative to base substitution alone. Applications of our approach include the generation of new protein folds and modeling the molecular evolution of disease.

Animals↗

PubMedDate not supplied

Monte Carlo methods for small molecule high-throughput experimentation.

By analogy with Monte Carlo algorithms, we propose new strategies for design and redesign of small molecule libraries in high-throughput experimentation, or combinatorial chemistry. Several Monte Carlo methods are examined, including Metropolis, three types of biased schemes, and composite moves that include swapping or parallel tempering. Among them, the biased Monte Carlo schemes exhibit particularly high efficiency in locating optimal compounds. The Monte Carlo strategies are compared to a genetic algorithm approach. Although the best compounds identified by the genetic algorithm are comparable to those from the better Monte Carlo schemes, the diversity of favorable compounds identified is reduced by roughly 60%.

Journal Article↗