Computer simulation of protein systems

Ligand binding to dihydrofolate reductase (DHFR) is discussed. This is an extremely important enzyme, as it is the target of several drugs (inhibitors) which are used clinically as antibacterials, antiprotozoals and in cancer chemotherapy. DHFR catalyzes the NADPH (reduced nicotinamide adenine dinucleotide phosphate) dependent reduction of dihydrofolate to tetrahydrofolate, which is used in several pathways of purine and pyrimidine iosynthesis, including that of thymidylate. Since DNA synthesis is dependent on a continuing supply of thymidylate, a blockade of DHFR resulting in a depletion of thymidylate can lead to the cessation of growth of a rapidly proliferating cell line. DHFR exhibits a significant species to species variability in its sensitivity to various inhibitors. For example, trimethoprim, an inhibitor of DHFR, binds to bacterial DHFR's 5 orders of magnitude greater than to vertebrate DHFR's. The structural mechanics, dynamics and energetics of a family of dihydrofolate reductases are studied to rationalize the basis for the inhibitor of these enyzmes and to understand the molecular basis of the difference in the binding constants between the species. This involves investigating the conformational changes induced in the protein on binding the ligand, the internal strain imposed by the enzyme on the ligand, the restriction of fluctuations in atom positions due to binding and the consequent change in entropy

Glycocalyx of Epidermal Cells in Vitro: Demonstration and Enzymatic Removal

Guinea-pig epidermal cells in culture possess a glycocalyx coat similar to that in vivo, as revealed by the ruthenium red staining technique. Trypsin. phospholipase C, and lysozyme do not produce any changes of the glycocalyx, while hyaluronidase and neuraminidase lead to partial and subcomplete removal, respectively. Cells stripped of their glycocalyx coat by neuraminidase do not detach from the support and do not show any signs of toxicity. There is complete reconstitution of the glycocalyx within 24 hr

Waste Not, Want Not: The Potential for Urban Water Conservation in California

The largest, least expensive, and most environmentally sound source of water to meet California's future needs is the water currently being wasted in every sector of our economy. This report, "Waste Not, Want Not," strongly indicates that California's urban water needs can be met into the foreseeable future by reducing water waste through cost-effective water-saving technologies, revised economic policies, appropriate state and local regulations, and public education

The olfactory basis of orchid pollination by mosquitoes.

Mosquitoes are important vectors of disease and require sources of carbohydrates for reproduction and survival. Unlike host-related behaviors of mosquitoes, comparatively less is understood about the mechanisms involved in nectar-feeding decisions, or how this sensory information is processed in the mosquito brain. Here we show that Aedes spp. mosquitoes, including Aedes aegypti, are effective pollinators of the Platanthera obtusata orchid, and demonstrate this mutualism is mediated by the orchid's scent and the balance of excitation and inhibition in the mosquito's antennal lobe (AL). The P. obtusata orchid emits an attractive, nonanal-rich scent, whereas related Platanthera species-not visited by mosquitoes-emit scents dominated by lilac aldehyde. Calcium imaging experiments in the mosquito AL revealed that nonanal and lilac aldehyde each respectively activate the LC2 and AM2 glomerulus, and remarkably, the AM2 glomerulus is also sensitive to N,N-diethyl-meta-toluamide (DEET), a mosquito repellent. Lateral inhibition between these 2 glomeruli reflects the level of attraction to the orchid scents. Whereas the enriched nonanal scent of P. obtusata activates the LC2 and suppresses AM2, the high level of lilac aldehyde in the other orchid scents inverts this pattern of glomerular activity, and behavioral attraction is lost. These results demonstrate the ecological importance of mosquitoes beyond operating as disease vectors and open the door toward understanding the neural basis of mosquito nectar-seeking behaviors

Critical Exponents of the Classical 3D Heisenberg Model: A Single-Cluster Monte Carlo Study

We have simulated the three-dimensional Heisenberg model on simple cubic lattices, using the single-cluster Monte Carlo update algorithm. The expected pronounced reduction of critical slowing down at the phase transition is verified. This allows simulations on significantly larger lattices than in previous studies and consequently a better control over systematic errors. In one set of simulations we employ the usual finite-size scaling methods to compute the critical exponents $\nu,\alpha,\beta,\gamma, \eta$ from a few measurements in the vicinity of the critical point, making extensive use of histogram reweighting and optimization techniques. In another set of simulations we report measurements of improved estimators for the spatial correlation length and the susceptibility in the high-temperature phase, obtained on lattices with up to $100^3$ spins. This enables us to compute independent estimates of $\nu$ and $\gamma$ from power-law fits of their critical divergencies.Comment: 33 pages, 12 figures (not included, available on request). Preprint FUB-HEP 19/92, HLRZ 77/92, September 199

The 2-dimensional non-linear sigma-model on a random latice

The O(n) non-linear $\sigma$-model is simulated on 2-dimensional regular and random lattices. We use two different levels of randomness in the construction of the random lattices and give a detailed explanation of the geometry of such lattices. In the simulations, we calculate the mass gap for $n=3, 4$ and 8, analysing the asymptotic scaling of the data and computing the ratio of Lambda parameters $\Lambda_{\rm random}/\Lambda_{\rm regular}$. These ratios are in agreement with previous semi-analytical calculations. We also numerically calculate the topological susceptibility by using the cooling method.Comment: REVTeX file, 23 pages. 13 postscript figures in a separate compressed tar fil