A Monte Carlo method for finding important ligand fragments from receptor data

A simulated annealing method for finding important ligand fragments is described. At a given temperature, ligand fragments are randomly selected and randomly placed within the given receptor cavity, often replacing or forming bonds with existing ligand fragments. For each new ligand fragment combination, the bonded, nonbonded, polarization and solvation energies of the new ligand–receptor system are compared to the previous configuration. Acceptance or rejection of the new system is decided using the Boltzmann distribution , where E is the energy difference between the old and new systems, k is the Boltzmann constant and T is the temperature. Thus, energetically unfavorable fragment switches are sometimes accepted, sacrificing immediate energy gains in the interest of finding a system with minimum energy. By lowering the temperature, the rate of unfavorable switches decreases and energetically favorable combinations become more difficult to change. The process is terminated when the frequency of switches becomes too small. As a test, the method predicted positions and types of important ligand fragments for neuraminidase that were in accord with the known ligand, sialic acid.     

Exact solutions of nonlinear generalizations of the wave equation

Exact solutions of nonlinear generalizations of the wave equation are constructed. In some cases these solutions are solitary waves or solitions. Thus, by explicit construction solitons or solitary waves are shown to exist in dispersionless systems. In contrast to previous solitary wave solutions, these solutions are limiting cases of solutions of nonlinear partial differential equations with dispersion.     

Equipment selection with heterogeneous fleets for multiple-period schedules

In a simple surface mining scenario we consider a mine to have one mining location and dumpsite connected by a truck route. We determine a purchase and salvage policy for trucks and loaders, which minimises the cost of materials handling over a multiple period schedule. This problem becomes large scale when we consider large sets of equipment and long schedules. Pre-existing equipment can lead to heterogeneous fleets; non-uniformity in the operating cost function coupled with compatibility issues also adds to the complexity of the problem. We present an integer programme for this problem, where we introduce a specialised linear constraint set to ensure satisfaction of production requirements while accounting for equipment compatibility. Many aspects of the presented model, such as the consideration of multiple periods and pre-existing equipment, are novel for the mining industry and ensure that the model is both a new and advanced equipment selection tool.     

Aperiodic interferometer for six degrees of freedom position measurement

We present a new class of interferometer system that is capable of simultaneous measurement of absolute position and rotation in all six degrees of freedom (DOF) with nanometer precision. This novel capability is due to the employment of a system of interference fringes that is not periodic. One of the key strengths offered by this new approach is that the absolute position of the system can be determined with a single measurement, rather than by counting fringes during displacement from a known location. The availability of a simultaneous measurement of all six DOF eliminates many problems associated with conventional interferometry.     

PHOTOSENSITIZATION BY DRUGS IN SURFACTANT SOLUTIONS

Abstract— Chlorpromazine, promazine, anthracene and furosemide were tested as photosensitizers using 365 nm UV light in micellar solutions of cationic, anionic and nonionic surfactants. In all cases, micelles enhanced the ability of these compounds to photosensitize the oxidation of 2,5-dimethylfuran and the free radical polymerization of acrylamide. pH variation showed that the base form of chlorpromazine and the acid form of furosemide are the principal photosensitizing forms of these compounds. Rate differences between cationic and anionic surfactant media indicate the cation radical to be the major photochemical species formed from chlorpromazine and promazine in micellar media. Photodechlorination of chlorpromazine accounted for a significantly higher reactivity of chlorpromazine over promazine. Anthracene was found to be a very active photosensitizer by the singlet oxygen mechanism but also yielded a small concentration of cation radicals in micellar solution. In its neutral form, furosemide reacted strongly in both photooxidation and photopolymerization systems.
The implications of this study to drug-induced photosensitivity are that (i) free radical reactions may play a major role, and (ii) these sensitizers are more reactive in a hydrophobic environment, suggesting that the cellular membrane or the hydrophobic surfaces of proteins or DNA are more important sites of action in photosensitivity.     

Ab initio study of catalyzed and uncatalyzed amide bond formation as a model for peptide bond formation: Ammonia-Glycine reactions

As a model reaction for peptide and bond formation, the S_N2 reactions between glycine and ammonia have been studied with and without amine catalysis: using ab initio molecular-orbital methods. For each of the catalyzed and uncatalyzed reactions, two reaction mechanisms have been examined: a two-step and a concerted mechanism. The stationary points of each reaction, including intermediate and transition states, have been identified and free energies calculated for all geometry-optimized reaction species to determine the thermodynamics and kinetics of the reaction. The calculations demonstrate that a second ammonia molecule catalyzes amide bond formation, and that the two-step mechanism is more favorable than the concerted one for the catalyzed reaction, while for the uncatalyzed reaction both mechanisms are competitive.