New Models and Insights

In this section we discuss new theory, as opposed to the new algorithms that are discussed in Section 11.4. Recent theoretical developments include new methods for incorporating salt effects into PCMs (Section 11.3.1) and new connections between PCM and generalized Born models (Section 11.3.2), which may help to improve the latter. 

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Thus, the chapters presented here are a microcosm of what the recent completion, or near completion, of various genome projects are enabling biochemists to understand not only about control and regulation of secondary metabolism, and how various pathways relate to each other, but also about its relation to primary metabolism. A major paradigm shift is occurring in the way we need to view secondary metabolism in the future. It is also clear that model systems, such as the ones discussed in the symposium, are providing new information and insight almost faster than we can process it ... 

Development of om models and screening methods is ongoing, and, in order to further develop and benchmark this method, we will rely on well-defined and well-characterized experiments, varying one parameter at the time. Our hope is that our simulations, in turn, wUl provide new insight and thereby give inspiration to new experiments. 

Further analysis yielded new models for each of the chemical classes with improved statistical significance. The final model for nonaromatics contained six descriptors and had an Rs of 0.932 (leave-one-out 0.878), the final model for the aromatics contained 21 descriptors and had an Rs of 0.942 (leave-one-out 0.823), and the final model for the heteroaromatics contained 13 descriptors and had an Rs value of 0.863 (leave-one-out 0.758). These statistical results were considered reliable enough for the models to be regarded as predictive. The analysis did yield some interesting insights into the impact of various structural fragments on human oral bioavailability. However, these observations were based on the sign of the coefficient and so must be treated with some caution. 

In the past decade, many new techniques have been developed and applied to the study of interfaces. While earlier measurements involved only macroscopic characteristics of the interface (e.g., surface charge, surface tension, and overall potential drop), new spectroscopic techniques have opened a window to the microstructure of the interface, and insight at the atomic level in this important region is now possible. Parallel to these discoveries and supported by them, more realistic theoretical models of the interface have been developed that combine quantum mechanical theories of metal surfaces and the statistical mechanics of solutions. 

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