David W. Deerfield

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A surge of development of new public health surveillance systems designed to provide more timely detection of outbreaks suggests that public health has a new requirement: extreme timeliness of detection. The authors review previous work relevant to measuring timeliness and to defining timeliness requirements. Using signal detection theory and decision(More)
We present an overview of multiple sequence alignments to outline the practical consequences for the choices among different techniques and parameters. We begin with a discussion of the scoring methods for quantifying the quality of a multiple sequence alignment, followed by a discussion of the algorithms implemented within a variety of multiple sequence(More)
Experimental structural data on the state of substrates bound to class 3 Aldehyde Dehydrogenases (ALDH3A1) is currently unknown. We have utilized molecular mechanics (MM) simulations, in conjunction with new force field parameters for aldehydes, to study the atomic details of benzaldehyde binding to ALDH3A1. Our results indicate that while the nucleophilic(More)
In this unit a protocol is described for predicting the structure of simple transmembrane a-helical bundles. The protocol is based on a global molecular dynamics search (GMDS) of the configuration space of the helical bundle, yielding several candidate structures. The correct structure among these candidates is selected using information from silent amino(More)
The interaction of organophosphate anions with divalent metal ions is central to many biological catalytic events. While experimental structural studies can give insight into the likely geometries that can be adopted, quantum mechanics allows for a more complete exploration of the competing forms. Ab initio quantum mechanical calculations have been(More)
Recent computer simulations of the cysteine nucleophilic attack on propanal in human mitochondrial aldehyde dehydrogenase (ALDH2) yielded an unexpected result: the chemically reasonable formation of a dead-end cysteine-cofactor adduct when NAD+ was in the "hydride transfer" position. More recently, this adduct found independent crystallographic support in(More)
Recent studies have shown that semiempirical methods (e.g., PM3 and AM1) for zinc-containing compounds are unreliable for modeling structures containing zinc ions with ligand environments similar to those observed in zinc metalloenzymes. To correct these deficiencies a reparameterization of zinc at the PM3 level was undertaken. In this effort we included(More)
We have studied the classification of the environment of residues within protein structures. Eisenberg's original idea created environmental categories to discriminate between similar residues [Bowie et al., Science (1991), 253, 164-170]. These environments grouped residues based upon their buried surface area, polarity of the surrounding environment, and(More)
A novel enzyme mechanism has been predicted by computer simulations for formation of the thiohemiacetal intermediate in the rat ALDH3A1 enzyme. We used molecular mechanics simulations to study the atomic details of substrate binding and quantum mechanical/molecular mechanical methods to study the Cys-243 thiolate attack on benzaldehyde (BA) substrate. BA(More)