Mark A McCoy

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Structural studies of protein-ligand complexes are often limited by low solubility, poor affinity, and interfacial motion and, in NMR structures, by the lack of intermolecular NOEs. In the absence of other structural restraints, we use a procedure that compares simulated chemical shift perturbations to observed perturbations to better define the binding(More)
NMR structures of protein-protein and protein-ligand complexes rely heavily on intermolecular NOEs. Recent work has shown that if no significant conformational changes occur upon complex formation residual dipolar coupling can replace most of the NOE restraints in protein-protein complexes, while restraints derived from chemical shift perturbations can(More)
The stabilization of p53 against Mdm2-mediated degradation is an important event in DNA damage response. Initial models of p53 stabilization focused on posttranslational modification of p53 that would disrupt the p53-Mdm2 interaction. The N-terminal regions of both p53 and Mdm2 are modified in vivo in response to cellular stress, suggesting that(More)
BACKGROUND The cost of pregnancy is increasing over time despite the decline in pregnancy rates. OBJECTIVE To fully elucidate and evaluate the cost drivers of pregnancy in the US for payers, a systematic review was conducted to understand the main cost components and primary factors that contribute to the direct costs of pregnancy, pregnancy-related(More)
Rapid, accurate structure determination of protein-ligand complexes is an essential component in structure-based drug design. We have developed a method that uses NMR protein chemical shift perturbations to spatially localize a ligand when it is complexed with a protein. Chemical shift perturbations on the protein arise primarily from the close proximity of(More)
The aim of this study is examine the impact of pregnancy and delivery complications on the healthcare costs of newborns during the first 3 months of life. We conducted a retrospective cohort study of newborns born to women ages 15–49 using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial Claims and Encounters database(More)
OBJECTIVES To identify the prevalence of comorbidities in pregnant women and examine the incremental costs of these conditions on the care for mothers and their newborns. METHODS This was a retrospective comparative cohort study of women ages 15-49 years with a documented live-birth delivery using de-identified claims from the MarketScan Research(More)
ATP-STD NMR takes advantage of Mg2+ binding to ATP to adjust the ATP affinity for protein kinases permitting a wide range of Ki's to be determined for ATP competitive ligands. Substituting Mn2+ for Mg2+ creates a paramagnetic probe (MnATP) from which the proximity of non-ATP competitive ligands can be inferred. Internal standards and references are used to(More)
The ribonucleotide reductase (RNR) enzyme is a heteromer of RRM1 and RRM2 subunits. The active enzyme catalyzes de novo reduction of ribonucleotides to generate deoxyribonucleotides (dNTPs), which are required for DNA replication and DNA repair processes. Complexity in the generation of physiologically relevant, active RRM1/RRM2 heterodimers was perceived(More)
OBJECTIVE To study the economic burden of pregnancy in the US, common complications during pregnancy, and the incremental costs attributable to these complications. METHODS A retrospective comparative cohort study was conducted of pregnant women aged 15-49 years using de-identified medical and pharmacy claims from the Truven Health MarketScan Commercial(More)