A novel and robust automated docking method that predicts the bound conformations of flexible ligands to macromolecular targets has been developed and tested, in combination with a new scoring function that estimates the free energy change upon binding. Interestingly, this method applies a Lamarckian model of genetics, in which environmental adaptations of an individual's phenotype are reverse transcribed into its genotype and become Ž . heritable traits sic . We consider three search methods, Monte Carlo simulated annealing, a traditional genetic algorithm, and the Lamarckian genetic algorithm, and compare their performance in dockings of seven protein᎐ligand test systems having known three-dimensional structure. We show that both the traditional and Lamarckian genetic algorithms can handle ligands with more degrees of freedom than the simulated annealing method used in earlier versions of AUTODOCK, and that the Lamarckian genetic algorithm is the most efficient, reliable, and successful of the three. The empirical free energy function was calibrated using a set of 30 structurally known protein᎐ligand complexes with experimentally determined binding constants. Linear regression analysis of the observed binding constants in terms of a wide variety of structure-derived molecular properties was performed. The final model had a residual standard y1 Ž y1 . error of 9.11 kJ mol 2.177 kcal mol and was chosen as the new energy

No abstract

No abstract

Following the events of September 11, 2001, in the United States, world public awareness for possible terrorist attacks on water supply systems has increased dramatically. Among the different threats for a water distribution system, the most difficult to address is a deliberate chemical or biological contaminant injection, due to both the uncertainty of the type of injected contaminant and its consequences, and the uncertainty of the time and location of the injection. An online contaminant monitoring system is considered as a major opportunity to protect against the impacts of a deliberate contaminant intrusion. However, although optimization models and solution algorithms have been developed for locating sensors, little is known about how these design algorithms compare to the efforts of

We describe Pyomo, an open source software package for modeling and solving mathematical programs in Python. Pyomo can be used to define abstract and concrete problems, create problem instances, and solve these instances with standard open-source and commercial solvers. Pyomo provides a capability that is commonly associated with algebraic modeling languages such as AMPL, AIMMS, and GAMS. In contrast, Pyomo's modeling objects are embedded within a full-featured highlevel programming language with a rich set of supporting libraries. Pyomo leverages the capabilities of the Coopr software library, which together with Pyomo is part of IBM's COIN-OR open-source initiative for operations research software. Coopr integrates Python packages for defining optimizers, modeling optimization applications, and managing computational experiments. Numerous examples illustrating advanced scripting applications are provided.

We present a mixed-integer programming (MIP) formulation for sensor placement optimization in municipal water distribution systems that includes the temporal characteristics of contamination events and their impacts. Typical network water quality simulations track contaminant concentration and movement over time, computing contaminant concentration time-series for each junction. Given this information, we can compute the impact of a contamination event over time and determine affected locations. This process quantifies the benefits of sensing contamination at different junctions in the network. Ours is the first MIP model to base sensor placement decisions on such data, compromising over many individual contamination events. The MIP formulation is mathematically equivalent to the well-known p-median facility location

No abstract

We present a model for optimizing the placement of sensors in municipal water networks to detect maliciously injected contaminants. An optimal sensor configuration minimizes the expected fraction of the population at risk. We formulate this problem as a mixed-integer program, which can be solved with generally available solvers. We find optimal sensor placements for three test networks with synthetic risk and population data. Our experiments illustrate that this formulation can be solved relatively quickly, and that the predicted sensor configuration is relatively insensitive to uncertainties in the data used for prediction.