Computational Design of Centralized HIV-1 Genes

2010 ◽  
Vol 8 (8) ◽  
pp. 613-621 ◽  
Author(s):  
Miguel Arenas ◽  
David Posada
Keyword(s):  
Computational Design ◽  
Hiv 1

scholarly journals Long antibody HCDR3s from HIV-naïve donors presented on a PG9 neutralizing antibody background mediate HIV neutralization

2016 ◽  
Vol 113 (16) ◽  
pp. 4446-4451 ◽  
Author(s):  
Jordan R. Willis ◽  
Jessica A. Finn ◽  
Bryan Briney ◽  
Gopal Sapparapu ◽  
Vidisha Singh ◽  
...  
Keyword(s):  
Amino Acid ◽  
Neutralizing Antibodies ◽  
Neutralizing Antibody ◽  
Computational Design ◽  
Cell Repertoire ◽  
B Cell Repertoire ◽  
Amino Acid Length ◽  
Massive Scale ◽  
Amino Acid Mutations ◽  
Hiv 1

Development of broadly neutralizing antibodies (bnAbs) against HIV-1 usually requires prolonged infection and induction of Abs with unusual features, such as long heavy-chain complementarity-determining region 3 (HCDR3) loops. Here we sought to determine whether the repertoires of HIV-1–naïve individuals contain Abs with long HCDR3 loops that could mediate HIV-1 neutralization. We interrogated at massive scale the structural properties of long Ab HCDR3 loops in HIV-1–naïve donors, searching for structured HCDR3s similar to those of the HIV-1 bnAb PG9. We determined the nucleotide sequences encoding 2.3 × 107unique HCDR3 amino acid regions from 70 different HIV-1–naïve donors. Of the 26,917 HCDR3 loops with 30-amino acid length identified, we tested 30 for further study that were predicted to have PG9-like structure when chimerized onto PG9. Three of these 30 PG9 chimeras bound to the HIV-1 gp120 monomer, and two were neutralizing. In addition, we found 14 naturally occurring HCDR3 sequences that acquired the ability to bind to the HIV-1 gp120 monomer when adding 2- to 7-amino acid mutations via computational design. Of those 14 designed Abs, 8 neutralized HIV-1, with IC50values ranging from 0.7 to 98 µg/mL. These data suggest that the repertoire of HIV-1–naïve individuals contains rare B cells that encode HCDR3 loops that bind or neutralize HIV-1 when presented on a PG9 background with relatively few or no additional mutations. Long HCDR3 sequences are present in the HIV-naïve B-cell repertoire, suggesting that this class of bnAbs is a favorable target for rationally designed preventative vaccine efforts.

scholarly journals Computational design of novel cyclic urea as HIV-1 protease inhibitor

2007 ◽  
Vol 5 (4) ◽  
pp. 1064-1072 ◽  
Author(s):  
Manga Vijjulatha ◽  
S. Kanth
Keyword(s):  
Biological Activity ◽  
Interaction Energy ◽  
Model Equation ◽  
Computational Design ◽  
Docking Studies ◽  
Computational Techniques ◽  
Ligand Interaction ◽  
Protein Ligand Interaction ◽  
Adme Properties ◽  
Hiv 1

AbstractA series of novel cyclic urea molecules 5,6-dihydroxy-1,3-diazepane-2,4,7-trione as HIV-1 protease inhibitors were designed using computational techniques. The designed molecules were compared with the known cyclic urea molecules by performing docking studies, calculating their ADME (Absorption, Distribution, Metabolism, and Excretion) properties and protein ligand interaction energy. These novel molecules were designed by substituting the P 1/P′ 1 positions (4th and 7th position of 1, 3-diazepan-2-one) with double bonded oxygens. This reduces the molecular weight and increases the bioavailability, indicating better ADME properties. The docking studies showed good binding affinity towards HIV-1 protease. The biological activity of these inhibitors were predicted by a model equation generated by the regression analysis between biological activity (log 1/K i ) of known inhibitors and their protein ligand interaction energy. The synthetic studies are in progress.

scholarly journals Computational design and clinical demonstration of a copper nanocluster based universal immunosensor for sensitive diagnostics

2020 ◽  
Vol 2 (1) ◽  
pp. 304-314 ◽  
Author(s):  
Aditya Dileep Kurdekar ◽  
Chelli Sai Manohar ◽  
L. A. Avinash Chunduri ◽  
Mohan Kumar Haleyurgirisetty ◽  
Indira K. Hewlett ◽  
...  
Keyword(s):  
Computational Design ◽  
Copper Nanoclusters ◽  
Hiv 1

Glutathione capped copper nanoclusters were bioconjugated to streptavidin protein using EDC-NHS coupling to engineer the Copper Nanocluster Immunosensor (CuNIS), which was tested for its efficiency by using HIV-1 p24 as the model analyte.

scholarly journals Towards conformational fidelity of a quaternary HIV-1 epitope: computational design and directed evolution of a minimal V1V2 antigen

2018 ◽  
Vol 31 (4) ◽  
pp. 121-133 ◽  
Author(s):  
Jennifer I Lai ◽  
Deeptak Verma ◽  
Chris Bailey-Kellogg ◽  
Margaret E Ackerman
Keyword(s):  
Directed Evolution ◽  
Computational Design ◽  
Hiv 1

Computational Design of New Cyclic Urea Inhibitors for Improved Binding of HIV-1 Aspartic Protease

2000 ◽  
Vol 268 (2) ◽  
pp. 384-389 ◽  
Author(s):  
Bhanuprakash Kotamarthi ◽  
Irena Bonin ◽  
Fabio Benedetti ◽  
Stanislav Miertus
Keyword(s):  
Computational Design ◽  
Aspartic Protease ◽  
Hiv 1

Computational design, synthesis and evaluation of new sulphonamide derivatives targeting HIV-1 gp120

2019 ◽  
Vol 34 (1) ◽  
pp. 39-54 ◽  
Author(s):  
Radhika Vangala ◽  
Sree Kanth Sivan ◽  
Saikiran Reddy Peddi ◽  
Vijjulatha Manga
Keyword(s):  
Computational Design ◽  
Design Synthesis ◽  
Computational Design Synthesis ◽  
Hiv 1

scholarly journals Tetrahydroxy Cyclic Urea-Potent Inhibitor for HIV-1 Protease Wild Type and Mutant Type—A Computational Design

2008 ◽  
Vol 5 (3) ◽  
pp. 584-592 ◽  
Author(s):  
S. Sree Kanth ◽  
M. Vijjulatha
Keyword(s):  
Biological Activity ◽  
Computational Design ◽  
Protein Docking ◽  
Hydroxyl Group ◽  
Computational Techniques ◽  
Wild Type ◽  
Type Protein ◽  
Wild Type Protein ◽  
Adme Properties ◽  
Hiv 1

A series of novel tetrahydroxy cyclic urea molecules as HIV-1 protease inhibitors were designed using computational techniques. The designed molecules were compared with the known cyclic urea molecules by performing docking studies on six of wild type protein and three mutant protein varieties and calculating their ADME properties. A series of novel molecules were designed by substituting hydrogen at the P1/ P1′ positions with hydroxyl group increasing the bioavailability these had better ADME properties and binding affinity towards HIV-1 protease. The biological activity of these inhibitors were predicted by a model equation generated by the regression analysis between biological activity (log 1/Ki) of known inhibitors and there combined docking scores from six of the wild type protein docking. The synthetic studies are in progress.

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