21 research outputs found
A method for validating the accuracy of NMR protein structures
We present a method that measures the accuracy of NMR protein structures. It compares random coil index [RCI] against local rigidity predicted by mathematical rigidity theory, calculated from NMR structures [FIRST], using a correlation score (which assesses secondary structure), and an RMSD score (which measures overall rigidity). We test its performance using: structures refined in explicit solvent, which are much better than unrefined structures; decoy structures generated for 89 NMR structures; and conventional predictors of accuracy such as number of restraints per residue, restraint violations, energy of structure, ensemble RMSD, Ramachandran distribution, and clashscore. Restraint violations and RMSD are poor measures of accuracy. Comparisons of NMR to crystal structures show that secondary structure is equally accurate, but crystal structures are typically too rigid in loops, whereas NMR structures are typically too floppy overall. We show that the method is a useful addition to existing measures of accuracy
Structural Polymorphism and Dynamism in the DNA Segment GATCTTCCCCCCGGAA: NMR Investigations of Hairpin, Dumbbell, Nicked Duplex, Parallel Strands, and i-Motif
Characterization of conformational features of DNA heteroduplexes containing aldehydic abasic sites
Sequence-Dependent Repair of Synthetic AP Sites in 15-mer and 35-mer Oligonucleotides: Role of Thermodynamic Stability Imposed by Neighbor Bases
Glycomimetic Ligands for the Human Asialoglycoprotein Receptor
The asialoglycoprotein receptor (ASGPR) is a high-capacity
galactose-binding
receptor expressed on hepatocytes that binds its native substrates
with low affinity. More potent ligands are of interest for hepatic
delivery of therapeutic agents. We report several classes of galactosyl
analogues with varied substitution at the anomeric, C2-, C5-, and
C6-positions. Significant increases in binding affinity were noted
for several trifluoromethylacetamide derivatives without covalent
attachment to the protein. A variety of new ligands were obtained
with affinity for ASGPR as good as or better than that of the parent <i>N</i>-acetylgalactosamine, showing that modification
on either side of the key C3,C4-diol moiety is well tolerated, consistent
with previous models of a shallow binding pocket. The galactosyl pyranose
motif therefore offers many opportunities for the attachment of other
functional units or payloads while retaining low-micromolar or better
affinity for the ASGPR
Structure-activity studies of peptides from the "hot-spot" region of human CD2 protein: Development of peptides for immunomodulation
10.1021/jm0503547Journal of Medicinal Chemistry48206236-6249JMCM
A Solid-State Deuterium NMR Study of the Localized Dynamics at the C9pG10 Step in the DNA Dodecamer [d(CGCGAATTCGCG)] 2
Generation of single-nucleotide repair patches following excision of uracil residues from DNA
Design and synthesis of truncated EGF-A peptides that restore LDL-R recycling in the presence of PCSK9 in vitro
Disrupting the binding interaction between proprotein convertase (PCSK9) and the epidermal growth factor-like domain A (EGF-A domain) in the low-density lipoprotein receptor (LDL-R) is a promising strategy to promote LDL-R recycling and thereby lower circulating cholesterol levels. In this study, truncated 26 amino acid EGF-A analogs were designed and synthesized, and their structures were analyzed in solution and in complex with PCSK9. The most potent peptide had an increased binding affinity for PCSK9 (K-D = 0.6 mu M) compared with wild-type EGF-A (K-D = 1.2 mu M), and the ability to increase LDL-R recycling in the presence of PCSK9 in a cell-based assay