A new method for exact analytical calculation of the accessible surface areas and their gradients with respect to atomic coordinates is described. The new surface routine, GETAREA, finds solvent‐exposed vertices of intersecting atoms, and thereby avoids calculating buried vertices which are not needed to determine the accessible surface area by the Gauss–Bonnet theorem. The surface routine was implemented in FANTOM, a program for energy minimization and Monte Carlo simulation, and tested for accuracy and efficiency in extensive energy minimizations of Met‐enkephalin, the α‐amylase inhibitor tendamistat, and avian pancreatic polypeptide (APP). The CPU time for the exact calculation of the accessible surface areas and their gradients has been reduced by factors of 2.2 (Met‐enkephalin) and 3.2 (tendamistat) compared with our previous approach. The efficiency of our exact method is similar to the recently described approximate methods MSEED and SASAD. The performance of several atomic solvation parameter sets was tested in searches for low energy conformations of APP among conformations near the native X‐ray crystal structure and highly distorted structures. The protein solvation parameters from Ooi et al. [Proc. Natl. Acad. Sci. USA, 84, 3086 (1987)] and from Wesson and Eisenberg [Prot. Sci., 1, 227 (1992)] showed a good correlation between solvation energies of the conformations and their root‐mean‐square deviations from the X‐ray crystal structure of APP. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 319–333, 1998

For classical TV-particle systems with pair interaction N" 1 X Φ(^ΐ~3j) trιe Vlasov dynamics is shown to be the w*-limit as l^i^J^N N-+QO. Propagation of molecular chaos holds in this limit, and the fluctuations of intensive observables converge to a Gaussian stochastic process.

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The current model of measles virus (MV) pathogenesis implies that apical infection of airway epithelial cells precedes systemic spread. An alternative model suggests that primarily infected lymphatic cells carry MV to the basolateral surface of epithelial cells, supporting MV shedding into the airway lumen and contagion. This model predicts that a mutant MV, unable to enter cells through the unidentified epithelial cell receptor (EpR), would remain virulent but not be shed. To test this model, we identified residues of the MV attachment protein sustaining EpR-mediated cell fusion. These nonpolar or uncharged polar residues defined an area located near the binding site of the signaling lymphocytic activation molecule (SLAM), the receptor for MV on lymphatic cells. We then generated an EpR-blind virus maintaining SLAM-dependent cell entry and inoculated rhesus monkeys intranasally. Hosts infected with the selectively EpR-blind MV developed rash and anorexia while averaging slightly lower viremia than hosts infected with wild-type MV but did not shed virus in the airways. The mechanism restricting shedding was characterized using primary well-differentiated human airway epithelial cells. Wild-type MV infected columnar epithelial cells bearing tight junctions only when applied basolaterally, while the EpR-blind virus did not infect these cells. Thus, EpR is probably a basolateral protein, and infection of the airway epithelium is not essential for systemic spread and virulence of MV.