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Tuberculosis and malaria together result in an estimated 5 million deaths annually. The spread of multidrug resistance in the most pathogenic causative agents, Mycobacterium tuberculosis and Plasmodium falciparum, underscores the need to identify active compounds with novel inhibitory properties. Although genetically unrelated, both organisms use a type II(More)
We have used molecular dynamics simulations to determine the stability in water of a model beta-sheet formed by two alanine dipeptide molecules with two intermolecular hydrogen bonds in the closely spaced antiparallel arrangement. In this paper we describe our computations of the binding free energy of the model sheet and a portion of the free energy(More)
We present the initial findings of a theoretical study of hydrogen bond formation between two formamide molecules in water and in carbon tetrachloride. These systems were chosen as the simplest models for secondary structure formation in the polar environment near the protein surface and the apolar environment of the protein interior. We have employed(More)
In order to investigate the role of nonpolar side chains in determining protein stability, we have carried out a molecular dynamics simulation study of the thermodynamics of interconverting isoleucine and valine side chains in the core of ribonuclease T1. The free energy change in the unfolded state, which we take to be fully solvated, was small and agrees(More)
A cost effective color graphics representation of molecular electrostatic potential surfaces employing the cumulative atomic or bond multipole moments has been described. A general description of the method used to obtain cumulative multipole moments directly from ab-initio wavefunctions is given, along with an outline of the algorithm for generating(More)
We have carried out molecular dynamics simulations to study the conformational equilibria of two blocked dipeptides, Ac-Ala-Ala-NHMe and trans-Ac-Pro-Ala-NHMe, in water (Ac, amino-terminal blocking group COCH3; NHMe, carboxy-terminal blocking group NHCH3). Using specialized sampling techniques we computed free-energy surfaces as functions of a conformation(More)
A series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid diamides that increase chloride transport in cells expressing mutant cystic fibrosis transmembrane conductance regulator (CFTR) protein has been identified from our compound library. Analoging efforts and the resulting structure-activity relationships uncovered are detailed. Compound potency was(More)
We describe a new classification of the amino acid side chains based on the potential energy level at which each will accept an extra (doublet) electron. The doublet acceptor energy level, and the doublet acceptor orbital were calculated using semiempirical INDO/2-UHF molecular orbital theory. The results of these calculations show that the side chains fall(More)
Software which permits an IBM AT and two IBM Professional Graphics Displays to be used to display high-quality three-dimensional space-filling stereoscopic images of macromolecules is described. Stereo image pairs generated on two screens are visually fused using a simple mirror system to provide binocular depth perception. Images are colored to identify(More)
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