We present an exposition of the various theoretical models currently in use for describing the dynamics of molecular dissociation at surfaces. We begin by outlining the representations of the nuclear and electronic dynamics and how these define the potential energy surfaces for the interactions. Strategies for solving the nuclear motion follow with particular emphasis being paid to a quantum description on the electronic ground state which is in line with experiments employing hyperthemal molecular beams. These can be performed in either a time-dependent or timeindependent fashion and both approaches are considered. Following this, the methods that have been developed for treating the dissipative motion as the molecule nears the surface are presented. This is divided into energy loss to the electronic subsystem and to the substrate atomic vibrations. The final part of the review shows how the results of theoretical simulations have been usefully applied to rationalize data obtained from molecular beam scattering experiments.

Oxamniquine resistance evolved in the human blood fluke (Schistosoma mansoni) in Brazil in the 1970s. We crossed parental parasites differing ~500-fold in drug response, determined drug sensitivity and marker segregation in clonally-derived F2s, and identified a single QTL (LOD=31) on chromosome 6. A sulfotransferase was identified as the causative gene using RNAi knockdown and biochemical complementation assays and we subsequently demonstrated independent origins of loss-of-function mutations in field-derived and laboratory-selected resistant parasites. These results demonstrate the utility of linkage mapping in a human helminth parasite, while crystallographic analyses of protein-drug interactions illuminate the mode of drug action and provide a framework for rational design of oxamniquine derivatives that kill both S. mansoni and S. haematobium, the two species responsible for >99% of schistosomiasis cases worldwide.

The human fungal pathogens Candida albicans and Histoplasma capsulatum have been reported to protect against the oxidative burst of host innate immune cells using a family of extracellular proteins with similarity to Cu/Zn superoxide dismutase 1 (SOD1). We report here that these molecules are widespread throughout fungi and deviate from canonical SOD1 at the primary, tertiary, and quaternary levels. The structure of C. albicans SOD5 reveals that although the β-barrel of Cu/Zn SODs is largely preserved, SOD5 is a monomeric copper protein that lacks a zinc-binding site and is missing the electrostatic loop element proposed to promote catalysis through superoxide guidance. Without an electrostatic loop, the copper site of SOD5 is not recessed and is readily accessible to bulk solvent. Despite these structural deviations, SOD5 has the capacity to disproportionate superoxide with kinetics that approach diffusion limits, similar to those of canonical SOD1. In cultures of C. albicans, SOD5 is secreted in a disulfide-oxidized form and apo-pools of secreted SOD5 can readily capture extracellular copper for rapid induction of enzyme activity. We suggest that the unusual attributes of SOD5-like fungal proteins, including the absence of zinc and an open active site that readily captures extracellular copper, make these SODs well suited to meet challenges in zinc and copper availability at the host-pathogen interface. E ukaryotes are known to express two highly related classes of copper-containing superoxide dismutase (SOD) enzymes that play widespread roles in oxidative stress resistance and signaling. These two classes include an intracellular, largely cytosolic SOD1 (1) and an extracellular SOD (EC-SOD) (2), both of which are bimetallic enzymes with copper and zinc cofactors. The redox active copper catalyzes the disproportionation of superoxide anion to oxygen and hydrogen peroxide, whereas the zinc helps stabilize the protein (3-5) and promotes pH independence of the reaction (6-8). Additionally, all eukaryotic copper and zinc SODs contain an active site channel that consists of a cluster of charges in loop VII that culminate with an invariant arginine adjacent to the copper site. This element, commonly known as the electrostatic loop, is proposed to provide long-and short-range guidance for the superoxide substrate, thereby facilitating the remarkable kinetics of the SOD reaction (2, 9, 10). SOD1 is among the fastest enzymes known, with rates (10 9 M −1 s −1 ) that approach diffusion limits (9, 11, 12). Very recently, certain pathogenic fungi have been reported to express a class of extracellular proteins that are homologous to SOD1 and are covalently attached to the cell wall through GPI anchors. These SODs were first described for the opportunistic fungal pathogen Candida albicans. C. albicans is a common commensal microbe of the human gut, but under conditions of a weakened immune system, the organism can become invasive and pathogenic, with infections ranging from mild mucosal candidiasis to life-threatening system...

The influence of rotational state on the dissociation probability of H2 on Cu(111) has been investigated with 3- and 4-dimensional close-coupling wave packet calculations. Recent experimental results have shown that the energetic threshold for dissociative adsorption increases and then decreases as the J state is continuously increased. This trend can be faithfully reproduced by modeling the H2 as a planar (cartwheel) rotor scattering from a flat surface. The agreement disappears when the model is extended to a 3-dimensional rotor. Further, the degenerate mJ states have a spread of dissociation probabilities which results in a broad smearing of the dissociation threshold. This effect, which is absent from experiment, increases with Ji. These shortcomings can be partially corrected by corrugating the potential in the azimuthal coordinate in accord with recent ab initio results. The dynamical calculations also exhibit strong rotational inelasticity for the scattered fraction, during dissociation. Since this system has a late barrier for dissociation, we show that the rotational inelasticity should be enhanced by initial vibrational state. Our 4-dimensional modeling is unable simultaneously to match the relative positions of dissociation and vibrational excitation thresholds. We speculate that these processes occur on different surface sites.

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