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PubMed2002

A large scale molecular dynamics simulation code using the fast multipole algorithm (FMD): performance and application.

We present the performance of the fast classical molecular dynamics (MD) code, fast molecular dynamics (FMD), designed for efficient, object-oriented, and scalable large scale simulations, and summarize its application to a liquid crystalline cluster. FMD uses an implementation of the three-dimensional fast multipole method, developed in our group. The fast multipole method offers an efficient way (order O(N)) to handle long range electrostatic interactions, thus, enabling more realistic simulations of large molecular systems. Performance testing was carried out on IBM SP2, SGI Origin 2000, and CRAY T3E massively parallel systems using the MPI massage passing library. The electrostatic forces were tested on models of up to 100,000 randomly placed charges, and on protein and liquid crystalline molecular systems of over 99,000 atoms. Tests on the stability of the method are presented, along with comparisons with direct calculations, the NAMD2 code, and the physical multipole-based cell-multipole method.

Algorithms↗

PubMed2002

Risk assessment of high-energy chemicals by in vitro toxicity screening and quantitative structure-activity relationships.

Hydrazine propellants pose a substantial operational concern to the U.S. Air Force and to the aerospace industry because of their toxicity. In our continuing efforts to develop methods for the prediction of the toxicological response to such materials, we have measured in vitro toxicity endpoints for a series of high-energy chemicals (HECs) that were recently proposed as propellants. The HECs considered are structurally diverse and can be classified into four chemical types (hydrazine-based, amino-based, triazoles, and a quaternary ammonium salt), although most are hydrazine derivatives. We measured the following endpoints in primary cultures of isolated rat hepatocytes: mitochondrial function (MTT), lactate dehydrogenase leakage (LDH), generation of reactive oxygen species (ROS), and total glutathione content (GSH). In several instances, effective concentrations (EC) were indeterminate, and only lower limits to the measured endpoints could be ascertained. Using molecular descriptors calculated with a semiempirical molecular orbital method, quantitative structure-activity relationships (QSARs) were derived for MTT (EC25) and for GSH (EC50). Correlation coefficients for 2- and 3-parameter QSARs of about 0.9 enable us to predict the toxicity for similar compounds. Furthermore, except in one case, predicted EC values for the uncertain endpoints were consistent with experiment. Descriptors comprising the QSARs for MTT were consistent with the biophysical mechanism of toxic response found experimentally for hydrazine derivatives. Application of our derived QSARs will assist in predicting toxicity for newly proposed propellants.

Aircraft↗