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

Signal processing in local neuronal circuits based on activity-dependent noise and competition

We study the characteristics of weak signal detection by a recurrent neuronal network with plastic synaptic coupling. It is shown that in the presence of an asynchronous component in synaptic transmission, the network acquires selectivity with respect to the frequency of weak periodic stimuli. For non-periodic frequency-modulated stimuli, the response is quantified by the mutual information between input (signal) and output (network's activity), and is optimized by synaptic depression. Introducing correlations in signal structure resulted in the decrease of input-output mutual information. Our results suggest that in neural systems with plastic connectivity, information is not merely carried passively by the signal; rather, the information content of the signal itself might determine the mode of its processing by a local neuronal circuit.Comment: 15 pages, 4 pages, in press for "Chaos

How Sustainable Are North American Wood Supplies?

This paper analyzes the current wood supply estimates for North America. The result of the analysis casts doubts whether the North American supplies are sustainable. It is obvious that current estimates do not consider many of the aspects of sustainable forest management but are based on a concept of the availability of timber. It can be concluded that there is a lack of consistent national projections in both the USA and Canada. The North American analyses do not take into account that the wood supply issue is driven by the political economy and not only by the market economy. North America has a lot to gain if future analyses of the supply would be carried out based on a political economic concept

First Calculation of Hyperon Axial Couplings from Lattice QCD

In this work, we report the first lattice calculation of hyperon axial couplings, using the 2+1-flavor MILC configurations and domain-wall fermion valence quarks. Both the $\Sigma$ and $\Xi$ axial couplings are computed for the first time in lattice QCD. In particular we find that $g_{\Sigma\Sigma} = 0.450(21)_{\rm stat}(27)_{\rm syst}$ and $g_{\Xi\Xi} = -0.277(15)_{\rm stat}(19)_{\rm syst}$.Comment: 5 pages, 2 figure