Journal: Viruses

Article Title: A Retrospective Analysis of Porcine Circovirus Type 3 in Samples Collected from 2008 to 2021 in Mexico

doi: 10.3390/v15112225

Figure Lengend Snippet: The phylogenetic tree using ORF2. The tree was obtained using multiple sequence alignment, and sequence comparisons were made in DNAstar Lasergene software version 17.3 and by the Randomized Accelerated Maximum Likelihood (RAxML) 1000 repetitions. Interactive Tree of Life (iTOL) was used for tree visualization. The scale bar indicates nucleotide substitutions per site. The sequences obtained in this study are highlighted in bold.

Article Snippet: Multiple sequence alignment and sequence comparisons were made in DNAstar Lasergene software version 17.3 (Madison, WI, USA) by 1000 repetitions of Randomized Accelerated Maximum Likelihood (RAxML).

Techniques: Sequencing, Software

Journal: Molecules

Article Title: Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [ 125 I]Radioiodinated DYRK1A Inhibitor

doi: 10.3390/molecules30050990

Figure Lengend Snippet: Phosphokinases and Tau phosphosites.

Article Snippet: Using Chimera-Autodock (version 1.17.3; 2023) as previously described for our experiments with Tau ligands [ ], DYRK1A (PDB 4YLL [ ]) was used to model the various molecules for DYRK1A binding energy calculations.

Techniques: Clinical Proteomics

Journal: Molecules

Article Title: Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [ 125 I]Radioiodinated DYRK1A Inhibitor

doi: 10.3390/molecules30050990

Figure Lengend Snippet: Schematic showing chromosome 21 with the Down’s syndrome critical region (DSCR) highlighted. Expression of DYRK1A is regulated by DSCR and is upregulated in Down’s syndrome (#1 blue dotted line). Membrane-bound DYRK1A may play a role in the hyperphosphorylation of Tau (#2 blue dotted line), resulting in the formation of neurofibrillary tangles (#3 blue dotted line). (Orange star: DYRK1A kinase; Green circles: normal Tau; Orange circles: phosphorylated Tau; Orange lines: Tau tangles).

Article Snippet: Using Chimera-Autodock (version 1.17.3; 2023) as previously described for our experiments with Tau ligands [ ], DYRK1A (PDB 4YLL [ ]) was used to model the various molecules for DYRK1A binding energy calculations.

Techniques: Expressing, Membrane

Journal: Molecules

Article Title: Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [ 125 I]Radioiodinated DYRK1A Inhibitor

doi: 10.3390/molecules30050990

Figure Lengend Snippet: Chemical structures of compounds with reported binding profiles. 1 . Harmine, binds to DYRK1A and MAO-A; 2 . 10-bromo-2-iodo-11 H -indolo[3,2-c]quinoline-6-carboxylic acid (4E3) binds to DYRK1A; 3 . 10-iodo-11 H -indolo[3,2-c]quinoline-6-carboxylic acid (KuFal184) binds to DYRK1A.

Article Snippet: Using Chimera-Autodock (version 1.17.3; 2023) as previously described for our experiments with Tau ligands [ ], DYRK1A (PDB 4YLL [ ]) was used to model the various molecules for DYRK1A binding energy calculations.

Techniques: Binding Assay

Journal: Molecules

Article Title: Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [ 125 I]Radioiodinated DYRK1A Inhibitor

doi: 10.3390/molecules30050990

Figure Lengend Snippet: DYRK1A and Tau binding energies of agents.

Article Snippet: Using Chimera-Autodock (version 1.17.3; 2023) as previously described for our experiments with Tau ligands [ ], DYRK1A (PDB 4YLL [ ]) was used to model the various molecules for DYRK1A binding energy calculations.

Techniques: Binding Assay

Journal: Molecules

Article Title: Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [ 125 I]Radioiodinated DYRK1A Inhibitor

doi: 10.3390/molecules30050990

Figure Lengend Snippet: ( A ). DYRK1A (PDB 4YLL protein structure used for binding energy measurements of various molecules; ( B ). Interaction of KuFAL184 at the binding site of DYRK1A. Three residues of DYRK1A binding site have been highlighted in red, including Leu241, Asp307, and Lys188. The high affinity of KuFal184 is driven by the “salt bridge” interaction between the carboxylate group in KuFal184 and Lys188.

Article Snippet: Using Chimera-Autodock (version 1.17.3; 2023) as previously described for our experiments with Tau ligands [ ], DYRK1A (PDB 4YLL [ ]) was used to model the various molecules for DYRK1A binding energy calculations.

Techniques: Binding Assay

Journal: Molecules

Article Title: Towards Imaging Tau Hyperphosphorylation: Is DYRK1A a Potential Target for Imaging Hyperphosphorylation of Tau? Molecular Modeling Assessment and Synthesis of [ 125 I]Radioiodinated DYRK1A Inhibitor

doi: 10.3390/molecules30050990

Figure Lengend Snippet: DYRK1A (PDB 4YLL ) Chimera-Autodock molecular models: energy-minimized comparative chemical structures in the binding site. ( A ). Energy-minimized comparison of KuFal184 and IPPI at the DYRK1A binding site; ( B ). Energy-minimized comparison of KuFal184 and MK-6240 at the DYRK1A binding site; ( C ). Energy-minimized comparison of harmine and IPPI at the DYRK1A binding site; ( D ). Energy-minimized comparison of harmine and MK-6240 at the DYRK1A binding site.

Article Snippet: Using Chimera-Autodock (version 1.17.3; 2023) as previously described for our experiments with Tau ligands [ ], DYRK1A (PDB 4YLL [ ]) was used to model the various molecules for DYRK1A binding energy calculations.

Techniques: Binding Assay, Comparison

Journal: Antibody Therapeutics

Article Title: Design of a chimeric ACE-2/Fc-silent fusion protein with ultrahigh affinity and neutralizing capacity for SARS-CoV-2 variants

doi: 10.1093/abt/tbad001

Figure Lengend Snippet: In silico testing of SARS CoV-2 Delta variant predicts Paradigm’s ACE-2 variant LVE/STR chimera out-scores competing ACE-2 chimeric technologies. Top panel: molecular modeling with Protean 3D Version 17.3 (DNASTAR. Madison, WI) software of ACE-2 LVE construct (green) binding to w.t. SARS-CoV-2 RBD (red) yields DFIRE score = −6.67. Bottom panel: identical modeling of ACE-2 LiVE construct (green) binding to SARS-CoV-2 Delta variant yields DFIRE score = −6.80, slightly tighter (stabilizing) than that for the w.t. RBD. Note rotation of RBD F456 (yellow) in Delta variant toward ACE-2 AA 27, made permissive by the T27L mutation.

Article Snippet: Molecular models were derived from publicly available ACE-2 and SARS-CoV-2 sequence databases ( Outbreak.info ) with Protean 3D Version 17.3 (DNASTAR.

Techniques: In Silico, Variant Assay, Software, Construct, Binding Assay, Mutagenesis

Journal: Antibody Therapeutics

Article Title: Design of a chimeric ACE-2/Fc-silent fusion protein with ultrahigh affinity and neutralizing capacity for SARS-CoV-2 variants

doi: 10.1093/abt/tbad001

Figure Lengend Snippet: Critical features of Paradigm’s chimeric ACE-2/Fc-silent antibody technology. These include: the use of a full length human ACE-2 domain (AAs 18–740, blue), which when modified as described next, substantially increases binding affinity for SARS CoV-2 RBD/spike protein (green); the choice of specific mutations in ACE-2 (top right red orange, light green AAs) that impart picomolar affinity for the RBD and ~ femtomolar affinity for the full-length spike protein; linkage of the ACE-2 construct to a completely Fc-silent “STR” mutated monoclonal antibody (yellow, Mike Clark PhD, used with permission). The use of STR technology in an ACE2 chimeric prophylactic for SARS CoV-2 is patent pending, see . In addition, one of the two mAb chimeras (“LiVE-Longer” vs. “LiVE”) utilizes a Y-T-E variant (red AAs, bottom) for increased half-life by binding to FcRn, which recycles IgG and is thereby predicted to increase its biological half-life by 3–4-fold (see and text for details). The “LiVE” mAB does not contain the YTE sequence; both LiVE and LiVE-Longer are tested in ( – and ). This figure was generated by Protean 3D, Version 17.3 (DNASTAR. Madison, WI).

Article Snippet: Molecular models were derived from publicly available ACE-2 and SARS-CoV-2 sequence databases ( Outbreak.info ) with Protean 3D Version 17.3 (DNASTAR.

Techniques: Modification, Binding Assay, Construct, Variant Assay, Sequencing, Generated

Journal: Antibody Therapeutics

Article Title: Design of a chimeric ACE-2/Fc-silent fusion protein with ultrahigh affinity and neutralizing capacity for SARS-CoV-2 variants

doi: 10.1093/abt/tbad001

Figure Lengend Snippet: The designed ACE-2 variant LVE/STR chimera scores higher than other ACE-2 Fusion protein competitors by the DFIRE scoring method. Molecular modeling was conducted with Protean 3D Version 17.3 (DNASTAR. Madison, WI) software, aimed at testing Paradigms’ proprietary LiVE variant (ACE-2 mutations T27L, H34V, and N90E) binding to w.t. SARS-2 RBD (DFIRE = −6.67), as it compares to the ACE-2 variant YTY (ACE-2 mutations T27Y, L79T and N330Y) binding to the w.t. SARS-2 RBD (DFIRE = −4.53). A lower DFIRE score predicts tighter (stabilizing) protein–protein interactions. See Methods for details.

Article Snippet: Molecular models were derived from publicly available ACE-2 and SARS-CoV-2 sequence databases ( Outbreak.info ) with Protean 3D Version 17.3 (DNASTAR.

Techniques: Variant Assay, Software, Binding Assay