PerspectiveTheoretical Chemistry Accounts © Springer-Verlag 2000Perspective on "Electrostatic interactions of a solute with a continuum. A direct utilization of ab initio molecular potentials for the prevision of solvent effects" Miertus S, Scrocco E, Tomasi J (1981) Chem Phys 55: 117Abstract. This paper provides an overview of the title paper by Miertus, Scrocco and Tomasi, including the impact that it has had on the theoretical description of solvation by means of continuum models.

This paper provides an overview of the title paper by Miertus, Scrocco and Tomasi, including the impact that it has had on the theoretical description of solvation by means of continuum models.

This study examines the accuracy of molecular dynamics-linear response (MD/LR) and Poisson± Boltzmann/solvent accessible surface (PB/SAS) calculations to predict relative binding anities. A series of acetylcholinesterase (AChE) huprine inhibitors has been chosen as a test system owing to the availability of freeenergy (thermodynamic integration) calculations. The results obtained with the MD/LR approach point out a clear relationship between the experimental anity and the electrostatic interaction energy alone for a subset of huprines, but the suitability of the MD/LR approach to predict the binding anity of the whole series of compounds is limited. On the other hand, PB/SAS calculations show a marked dependence on both the computational protocol and the nature of the inhibitor± enzyme complex.

The tautomeric preferences of cytosine and its derivatives substituted at position 5 (R ) CH 3 , propynyl, Cl, and Br) have been analyzed both in the gas phase and in aqueous solution by using a combination of stateof-the-art theoretical methods. It is found that 5-substitutions do not alter dramatically the tautomeric preferences of cytosine in gas phase or aqueous solution. The Hoogsteen-type hydrogen-bonding and stacking properties of the imino form of cytosine and its substituted derivatives are examined in light of the results determined by using ab initio quantum mechanical and density functional calculations. It is found that imino cytosines, and especially its 5-propynyl and 5-Br derivatives show very good stacking in triplexes. The impact of the results in the design of new pyrimidines with ambiguous Hoogsteen pairing ability for the stabilization of triple helices is discussed.

Fault Tree Analysis (FTA) is a wellestablished technique to analyze the safety risks of a system. Two specific prominent FTA methods, largely applied in the aerospace field, are the socalled Minimal Cut Sets (MCS), which uses an approximate evaluation of the problem, and the Direct Evaluation (DE) of the fault tree, which uses a top-down recursive algorithm. The first approach is only valid for small values of basic event probabilities and has historically yielded faster results than exact solutions for complex fault trees. The second one means exact solutions at a higher computational cost. The paper presents several improvements applied to both approaches in order to upgrade the computing performance. Firstly, improvements to the MCS approach have been performed, where the main idea has been to optimize the number of required permutations and to take advantage of the available information from previous solved subsets. Secondly, improvements to the DE approach have been applied, which deal with a reduction of the number of recursive calls through a deep search for independent events in the fault tree. This could dramatically reduce the computation time for industrial fault trees with a high number of repeated events.