Hugh B. Nicholas

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One hundred-forty-five full-length aldehyde dehydrogenase-related sequences were aligned to determine relationships within the aldehyde dehydrogenase (ALDH) extended family. The alignment reveals only four invariant residues: two glycines, a phenylalanine involved in NAD binding, and a glutamic acid that coordinates the nicotinamide ribose in certain E-NAD(More)
Sequences of 16 NAD and/or NADP-linked aldehyde oxidoreductases are aligned, including representative examples of all aldehyde dehydrogenase forms with wide substrate preferences as well as additional types with distinct specificities for certain metabolic aldehyde intermediates, particularly semialdehydes, yielding pairwise identities from 15 to 83%.(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)
We have developed a two-level case-based reasoning architecture for predicting protein secondary structure. The central idea is to break the problem into two levels: first, reasoning at the object (protein) level, and using the global information from this level to focus on a more restricted problem space; second, decomposing objects into pieces (segments),(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)
Computer-assisted comparisons of 67 tRNA sequences that function in Escherichia coli or Salmonella typhimurium were used to identify single and multiple nucleotide positions that maximally distinguish the 20 amino acid acceptor groups. Positions in the anticodon were identified most frequently, as expected from the decoding function of this region of the(More)
Molecular dynamics (MD) simulation of the rat class 3 aldehyde dehydrogenase (ALDH) with nicotinamide dinucleotide (NAD) cofactors and explicit water molecules are reported. Our results demonstrate that MD simulation using the latest methodologies can maintain the crystal structure of the enzyme, as well as closely reproduce the short timescale dynamics of(More)
Procaryotic and eucaryotic transfer RNA sequences are distinct at the 0.5% probability level as demonstrated by permutation testing. Moreover, within each cell type, transfer RNA sequences of different amino acid acceptor classes are distinct at the 0.1% level. We propose that the latter finding reflects sets of nucleotides, other than the anticodons(More)