Molecular computations for reactions and phase transitions: applications to protein stabilization, hydrates and catalysis

In this work we have made significant contributions in three different areas of interest: therapeutic protein stabilization, thermodynamics of natural gas clathrate-hydrates, and zeolite catalysis. In all three fields, using our various computational techniques, we have been able to elucidate phenomena that are difficult or impossible to explain experimentally. More specifically, in mixed solvent systems for proteins we developed a statistical-mechanical method to model the thermodynamic effects of additives in molecular-level detail. It was the first method demonstrated to have truly predictive (no adjustable parameters) capability for real protein systems. We also describe a novel mechanism that slows protein association reactions, called the “gap effect.” We developed a comprehensive picture of methioine oxidation by hydrogen peroxide that allows for accurate prediction of protein oxidation and provides a rationale for developing strategies to control oxidation. The method of solvent accessible area (SAA) was shown not to correlate well with oxidation rates. A new property, averaged two-shell water coordination number (2SWCN) was identified and shown to correlate well with oxidation rates. Reference parameters for the van der Waals Platteeuw model of clathrate-hydrates were found for structure I and structure II. These reference parameters are independent of the potential form (unlike the commonly used parameters) and have been validated by calculating phase behavior and structural transitions for mixed hydrate systems. These calculations are validated with experimental data for both structures and for systems that undergo transitions from one structure to another. This is the first method of calculating hydrate thermodynamics to demonstrate predictive capability for phase equilibria, structural changes, and occupancy in pure and mixed hydrate systems. We have computed a new mechanism for the methanol coupling reaction to form ethanol and water in the zeolite chabazite. The mechanism at 400°C proceeds via stable intermediates of water, methane, and protonated formaldehyde.

The Role of Chemical Mechanisms in Neural Computation and Learning

Most computational models of neurons assume that their electrical characteristics are of paramount importance. However, all long-term changes in synaptic efficacy, as well as many short-term effects, are mediated by chemical mechanisms. This technical report explores the interaction between electrical and chemical mechanisms in neural learning and development. Two neural systems that exemplify this interaction are described and modelled. The first is the mechanisms underlying habituation, sensitization, and associative learning in the gill withdrawal reflex circuit in Aplysia, a marine snail. The second is the formation of retinotopic projections in the early visual pathway during embryonic development.

Computation and Pre-Parametric Design

My work is broadly concerned with the question "How can designs bessynthesized computationally?" The project deals primarily with mechanical devices and focuses on pre-parametric design: design at the level of detail of a blackboard sketch rather than at the level of detail of an engineering drawing. I explore the project ideas in the domain of single-input single-output dynamic systems, like pressure gauges, accelerometers, and pneumatic cylinders. The problem solution consists of two steps: 1) generate a schematic description of the device in terms of idealized functional elements, and then 2) from the schematic description generate a physical description.

ADAM: A Decentralized Parallel Computer Architecture Featuring Fast Thread and Data Migration and a Uniform Hardware Abstraction

The furious pace of Moore's Law is driving computer architecture into a realm where the the speed of light is the dominant factor in system latencies. The number of clock cycles to span a chip are increasing, while the number of bits that can be accessed within a clock cycle is decreasing. Hence, it is becoming more difficult to hide latency. One alternative solution is to reduce latency by migrating threads and data, but the overhead of existing implementations has previously made migration an unserviceable solution so far. I present an architecture, implementation, and mechanisms that reduces the overhead of migration to the point where migration is a viable supplement to other latency hiding mechanisms, such as multithreading. The architecture is abstract, and presents programmers with a simple, uniform fine-grained multithreaded parallel programming model with implicit memory management. In other words, the spatial nature and implementation details (such as the number of processors) of a parallel machine are entirely hidden from the programmer. Compiler writers are encouraged to devise programming languages for the machine that guide a programmer to express their ideas in terms of objects, since objects exhibit an inherent physical locality of data and code. The machine implementation can then leverage this locality to automatically distribute data and threads across the physical machine by using a set of high performance migration mechanisms. An implementation of this architecture could migrate a null thread in 66 cycles -- over a factor of 1000 improvement over previous work. Performance also scales well; the time required to move a typical thread is only 4 to 5 times that of a null thread. Data migration performance is similar, and scales linearly with data block size. Since the performance of the migration mechanism is on par with that of an L2 cache, the implementation simulated in my work has no data caches and relies instead on multithreading and the migration mechanism to hide and reduce access latencies.

Context Mediation in the Semantic Web: Handling OWL Ontology and Data Disparity through Context Interchange

The COntext INterchange (COIN) strategy is an approach to solving the problem of interoperability of semantically heterogeneous data sources through context mediation. COIN has used its own notation and syntax for representing ontologies. More recently, the OWL Web Ontology Language is becoming established as the W3C recommended ontology language. We propose the use of the COIN strategy to solve context disparity and ontology interoperability problems in the emerging Semantic Web – both at the ontology level and at the data level. In conjunction with this, we propose a version of the COIN ontology model that uses OWL and the emerging rules interchange language, RuleML.

Intelligence in Scientific Computing

Combining numerical techniques with ideas from symbolic computation and with methods incorporating knowledge of science and mathematics leads to a new category of intelligent computational tools for scientists and engineers. These tools autonomously prepare simulation experiments from high-level specifications of physical models. For computationally intensive experiments, they automatically design special-purpose numerical engines optimized to perform the necessary computations. They actively monitor numerical and physical experiments. They interpret experimental data and formulate numerical results in qualitative terms. They enable their human users to control computational experiments in terms of high-level behavioral descriptions.