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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)
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)
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)
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)
The first direct equilibrium dialysis titration of the blood coagulation protein bovine prothrombin fragment 1 with Mg(II) is presented. Fragment 1 has fewer thermodynamic binding sites for Mg(II) than Ca(II), less overall binding affinity, and significantly less cooperativity. Several nonlinear curve fitting models were tested for describing the binding of(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)
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)
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 provide a detailed overview of the choices inherent in performing a sequence database search, including the choice of algorithm, substitution matrix and gap model. Each of these choices has implications that can be described as restrictions on the underlying model of sequence evolution, the expected degree of divergence between the query sequence and the(More)