Crystal Structure of Monoclonal 6B5 Fab Complexed with Phencyclidine

The crystal structure of monoclonal antibody (mAb) 6B5 Fab fragment complexed with 1-(1-phenylcyclohexyl)piperidine (PCP or phencyclidine) was determined at 2.2-A resolution. 6B5 was originally produced from a mouse immunized with a phencyclidine analogue hapten 5-[N-(1'phenylcyclohexyl)amino]pentanoic acid conjugated to bovine serum albumin. This mAb was selected for further study because of its high affinity (Kd = 2 x 10(-9) M/liter) for PCP and usefulness in reversing PCP-induced central nervous system toxicity in laboratory animals. The dominant feature of the 6B5 Fab.PCP complex is the deep binding site and hydrophobic nature of the interaction. The ligand binding pocket of 6B5 Fab has numerous aromatic side chains, as compared with other known Fab structures. The most notable feature of the binding site is a Trp at position 97H (H-chain), and the side chain of this residue appears to act as a hydrophobic umbrella on the ligand in the antigen binding pocket. There are only two other known Fabs found with a Trp at the 97H position in complementarity determining region (CDR) H3, but they do not play a major role in the interaction with their respective antigens; in both Fab TE33 and R6.5 the Trp 97H side chain is positioned away from the bound antigen. Comparison of the CDR residues of 6B5 with other Fab structures with similar CDR sizes and amino acid compositions reveals a number of important patterns of residue substitutions that appear to be critical for specific PCP ligand interactions

Tactical and Strategic Communication Network Simulation and Performance Analysis

We describe a framework for the efficient modeling and performance evaluation of large networks consisting of mixture of strategic and tactical components. The method emphasizes hierarchical, layered techniques that are fed parametric models at the lower level. In addition to the algorithmic structure, and some initial algorithms we describe an object oriented software architecture that is under development to support these algorithmic methods in a distributed environment

Rarely pure and never simple: Assessing cumulative evidence in strategic management

As empirical evidence in strategy has accumulated, scholars have shown increasing interest in assessing the empirical record of leading theories. Two methods of assessment have figured prominently: vote counting and meta-analysis. Recently, critics have denounced the former in favor of the latter. While meta-analysis is certainly a powerful assessment tool, we argue that both vote counting and meta-analysis are characterized by certain strengths and weaknesses and that these methods should be seen as complementary means of understanding bodies of empirical evidence. We provide guidance regarding when to employ each method and how to improve the process of cumulative assessment.</jats:p