A5009857117- Computational Drug Discovery Methods
- Protein Structure and Dynamics
- Monoclonal and Polyclonal Antibodies Research
- Bioinformatics and Genomic Networks
- Enzyme Structure and Function
- Gene expression and cancer classification
- HIV/AIDS drug development and treatment
- HIV Research and Treatment
- Microtubule and mitosis dynamics
- Microbial Natural Products and Biosynthesis
- Protein purification and stability
- Burkholderia infections and melioidosis
- Cancer Treatment and Pharmacology
- Click Chemistry and Applications
- Spectroscopy and Quantum Chemical Studies
- Radiopharmaceutical Chemistry and Applications
- Glycosylation and Glycoproteins Research
- DNA and Nucleic Acid Chemistry
- Toxin Mechanisms and Immunotoxins
- Marine Sponges and Natural Products
- Pharmacogenetics and Drug Metabolism
- Chemical Synthesis and Analysis
- Bayesian Methods and Mixture Models
- Bacteriophages and microbial interactions
- Molecular Biology Techniques and Applications
National Cancer Institute
2007-2021
Frederick National Laboratory for Cancer Research
1994-2013
National Institutes of Health
1990-2012
Target (United States)
2009
Center for Cancer Research
2001-2008
Science Applications International Corporation (United States)
1997-2007
NeuroDevelopment Center
2006
Sabancı Üniversitesi
1999
Boğaziçi University
1998-1999
Scientific and Technological Research Council of Turkey
1998-1999
We studied the self-reported information needs of 47 physicians during a half day typical office practice. The raised 269 questions about patient management. Questions related to all medical specialties and were highly specific individual patient's problem. Subspecialists most frequently asked other subspecialties. Only 30% physicians' met visit, usually by another physician or health professional. Reasons print sources not used included age textbooks in office, poor organization journal...
Abstract The role of hydrophobicity as a determinant protein‐protein interactions is examined. Surfaces apo‐protein targets comprising 9 classes enzymes, 7 antibody fragments, hirudin, growth hormone, and retinol‐binding protein, their associated ligands with available X‐ray structures for complexed forms, are scanned to determine clusters surface‐accessible amino acids. Clusters surface residues ranked on the basis constituent results indicate that location co‐crystallized ligand commonly...
The reaction of the human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein p7 (NCp7) with a variety electrophilic agents was investigated by experimental measurements Trp37 fluorescence decay and compared theoretical measures reactivity based on density-functional theory in context hard soft acids bases principle. Statistically significant correlations were found between rates ability these to function as electrophiles. Notably, molecular property that correlated strongest ratio...
ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTHydrophobic Interactions in Aqueous Urea Solutions with Implications for the Mechanism of Protein DenaturationA. Wallqvist, D. G. Covell, and ThirumalaiView Author Information Frederick Cancer Research Development Center National Institute Science Applications International Corporation Maryland 21702 Department Chemistry Biochemistry Physical Technology University College Park, 20742 Cite this: J. Am. Chem. Soc. 1998, 120, 2,...
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTConformations of folded proteins in restricted spacesDavid G. Covell and Robert L. JerniganCite this: Biochemistry 1990, 29, 13, 3287–3294Publication Date (Print):April 3, 1990Publication History Published online1 May 2002Published inissue 3 April 1990https://pubs.acs.org/doi/10.1021/bi00465a020https://doi.org/10.1021/bi00465a020research-articleACS PublicationsRequest reuse permissionsArticle Views150Altmetric-Citations178LEARN ABOUT THESE...
An extract from Phyllanthus engleri was identified in a bioinformatic analysis of NCI 60-cell natural product screening data that selectively inhibited the growth renal cancer cell lines. Bioassay-guided fractionation yielded two new guaiane sesquiterpenes, englerins A (1) and B (2). Englerin showed 1000-fold selectivity against six eight lines with GI50 values ranging 1−87 nM. The structures 1 2 their relative stereochemistry were established by spectroscopic methods.
Recently, we developed a simple analytical model based on local residue packing densities and the distribution of tertiary contacts for describing conformational fluctuations proteins in their folded state. This so-called Gaussian network (GNM) is applied here to interpretation experimental hydrogen exchange (HX) behavior native state or under weakly denaturing conditions. Calculations are performed five proteins: bovine pancreatic trypsin inhibitor, cytochrome c, plastocyanin,...
The dynamics of the GroEL-GroES complex is investigated with a coarse-grained model. This model one in which single-residue points are connected to other such points, nearby, by identical springs, forming network interactions. nature most important (slowest) normal modes reveals wide variety motions uniquely dependent upon central cavity structure, including opposed torsional rotation two GroEL rings accompanied alternating compression and expansion GroES cap binding region, bending, shear,...
The chemical stability of 207 zinc fingers, derived from 92 experimental protein structures, is evaluated according to the packing and electrostatic screening their cores. These properties are used as measures protection cores, predictively rank relative finger reactivities assess differences in function. On average, there a substantial concomitant increase increasingly anionic core motifs, suggesting fingers have evolved manner that promotes shielding potentially reactive thiolates. In...
ADVERTISEMENT RETURN TO ISSUEPREVArticleRaman spectroscopy of synthetic antimicrobial frog peptides magainin 2a and PGLaRobert W. Williams, Ruth Starman, Kenneth M. P. Taylor, Gable, Troy Beeler, Michael Zasloff, David CovellCite this: Biochemistry 1990, 29, 18, 4490–4496Publication Date (Print):May 8, 1990Publication History Published online1 May 2002Published inissue 8 1990https://pubs.acs.org/doi/10.1021/bi00470a031https://doi.org/10.1021/bi00470a031research-articleACS PublicationsRequest...
We have studied fusion between membranes of vesicular stomatitis virus (VSV) and Vero cells using an assay for lipid mixing based on the relief self-quenching octadecylrhodamine (R18) fluorescence. could identify two pathways by kinetics R18 dequenching, effects inhibitors, temperature dependence, dependence osmotic pressure. Fusion at plasma membrane began immediately after lowering pH below 6 showed approximately exponential time course, whereas via endocytic pathway (pH 7.4) became...
In an effort to enhance access information available in the National Cancer Institute's (NCI) anticancer drug-screening database, a new suite of Internet accessible (http://spheroid. ncifcrf.gov) computational tools has been assembled for self-organizing map-based (SOM) cluster analysis and data visualization. A range questions were initially addressed evaluate improvements SOM quality based on data-conditioning procedures Z-score normalization, capping, treatment missing as well...
Agents that target the two highly conserved Zn fingers of human immunodeficiency virus (HIV) nucleocapsid p7 (NCp7) protein are under development as antivirals. These agents covalently modify Zn-coordinating cysteine thiolates fingers, causing ejection, loss native structure and nucleic acid binding capacity, disruption replication. Concentrations three antiviral promoted in vitro ejection from NCp7 inhibited HIV replication did not impact functions cellular finger proteins, including...
The interface between protein receptor-ligand complexes has been studied with respect to their binary interatomic interactions. Crystal structure data have used catalogue surfaces buried by atoms from each member of a bound complex and determine statistical preference for pairs amino-acid atoms. A simple free energy model the system is constructed these atom-atom preferences assess energetic importance interfacial approximation binding strength in this reliability about ±1.5 kcal/mol,...
Nucleocapsid p7 protein (NCp7) zinc finger domains of the human immunodeficiency virus type 1 (HIV-1) are being developed as antiviral targets due to their key roles in viral replication and mutationally nonpermissive nature. On basis our experience with symmetrical disulfide benzamides (DIBAs; Rice et al. Science 1995, 270, 1194−1197), we synthesized evaluated variants these dimers, including sets 4,4'- 3,3'-disubstituted diphenyl sulfones monomeric benzisothiazolone derivatives (BITA)....