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Crystallographic studies have shown that the binding of calcium to domain III of annexin V is accompanied by a large conformational change involving surface exposure of Trp187. Here we examine this conformational transition using computer simulation. It is found that the burial of Trp187 is accompanied by a large increase in conformational strain,(More)
Structure-based drug design is now well-established for proteins as a key first step in the lengthy process of developing new drugs. In many ways, RNA may be a better target to treat disease than a protein because it is upstream in the translation pathway, so inhibiting a single mRNA molecule could prevent the production of thousands of protein gene(More)
BACKGROUND Chagas Disease is the leading cause of heart failure in Latin America. Current drug therapy is limited by issues of both efficacy and severe side effects. Trypansoma cruzi, the protozoan agent of Chagas Disease, is closely related to two other major global pathogens, Leishmania spp., responsible for leishmaniasis, and Trypansoma brucei, the(More)
It is still difficult to obtain a precise structural description of the transition between the deoxy T-state and oxy R-state conformations of human hemoglobin, despite a large number of experimental studies. We used molecular dynamics with the Path Exploration with Distance Constraints (PEDC) method to provide new insights into the allosteric mechanism at(More)
A set of protein fragments was produced by site-directed mutagenesis followed by chemical cleavage of phosphoglycerate kinase according to a previously described method [Pecorari et al. (1993) Protein Eng. 6, 313-325]. The cleavage positions were chosen in order to correspond to limits between structural subdomains. These isolated fragments were studied by(More)
A method to find low energy paths in macromolecules is described. It can be applied either to determine paths between two given energy minimum conformations, or to explore low energy paths departing from one energy minimized conformation. The principle of the method consists in carrying out energy minimizations or molecular dynamics simulations with root(More)
Conformational flexibility in the prion protein is believed to play a role in prion diseases. Here we examine the dynamic structure of the mouse cellular prion protein using two one-nanosecond molecular dynamics simulations from different initial conditions. The two simulations produce similar results. The overall structure remains close to that determined(More)
The human ribonucleoprotein telomerase is a validated anticancer drug target, and hTR-P2b is a part of the human telomerase RNA (hTR) essential for its activity. Interesting ligands that bind hTR-P2b were identified by iteratively using a tandem structure-based approach: docking of potential ligands from small databases to hTR-P2b via the program MORDOR,(More)
We present the results of two 1.2 ns molecular dynamics (MD) unfolding simulations on hen egg lysozyme in water at 300K, performed using a new procedure called PEDC (Path Exploration With Distance Constraints). This procedure allows exploration of low energy structures as a function of increasing RMSD from the native structure, and offers especially the(More)
In strong alkali, nicotinamide adenine dinucleotide (NAD+) undergoes a ring opening of the nicotinamide ring. The open form of NAD+, ONAD, has two pKa values at--1.9 and 11.2 and absorbs maximally at 350 nm in its acidic form, at 372 nm in its neutral form, and at 340 nm in its aniomic form. ONAD has the chemical properties expected for a Schiff base of(More)