Understanding the Basis of Resistance in the Irksome Lys103Asn HIV-1 Reverse Transcriptase Mutant through Targeted Molecular Dynamics Simulations

2004 ◽  
Vol 126 (47) ◽  
pp. 15386-15387 ◽  
Author(s):  
Fátima Rodríguez-Barrios ◽  
Federico Gago
Keyword(s):  
Molecular Dynamics ◽  
Reverse Transcriptase ◽  
Molecular Dynamics Simulations ◽  
Targeted Molecular Dynamics ◽  
Dynamics Simulations ◽  
Hiv 1

scholarly journals Computational development of rubromycin-based lead compounds for HIV-1 reverse transcriptase inhibition

2014 ◽  
Author(s):  
Pedro J Silva ◽  
Carlos E. P. Bernardo
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Molecular Dynamics Simulations ◽  
Complex Interplay ◽  
Lead Compounds ◽  
High Affinity ◽  
Dynamics Simulations ◽  
Hiv 1

The binding of several rubromycin-based ligands to HIV1-reverse transcriptase was analyzed using molecular docking and molecular dynamics simulations. MM-PBSA analysis and examination of the trajectories allowed the identification of several promising compounds with predicted high affinity towards reverse transcriptase mutants which have proven resistant to current drugs. Important insights on the complex interplay of factors determining the ability of ligands to selectively target each mutant have been obtained.

scholarly journals Computational development of rubromycin-based lead compounds for HIV-1 reverse transcriptase inhibition

2014 ◽  
Author(s):  
Pedro J Silva ◽  
Carlos E. P. Bernardo
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Reverse Transcriptase ◽  
Molecular Dynamics Simulations ◽  
Complex Interplay ◽  
Lead Compounds ◽  
High Affinity ◽  
Dynamics Simulations ◽  
Hiv 1

The binding of several rubromycin-based ligands to HIV1-reverse transcriptase was analyzed using molecular docking and molecular dynamics simulations. MM-PBSA analysis and examination of the trajectories allowed the identification of several promising compounds with predicted high affinity towards reverse transcriptase mutants which have proven resistant to current drugs. Important insights on the complex interplay of factors determining the ability of ligands to selectively target each mutant have been obtained.

Insight into HIV-1 reverse transcriptase–aptamer interaction from molecular dynamics simulations

2014 ◽  
Vol 20 (8) ◽  
Author(s):  
Niran Aeksiri ◽  
Napat Songtawee ◽  
M. Paul Gleeson ◽  
Supa Hannongbua ◽  
Kiattawee Choowongkomon
Keyword(s):  
Molecular Dynamics ◽  
Reverse Transcriptase ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulations ◽  
Insight Into ◽  
Hiv 1

scholarly journals Molecular Dynamics Simulations of the First Steps of the Reaction Catalyzed by HIV-1 Protease

2002 ◽  
Vol 83 (2) ◽  
pp. 794-807 ◽  
Author(s):  
Joanna Trylska ◽  
Piotr Bała ◽  
Maciej Geller ◽  
Paweł Grochowski
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Dynamics Simulations ◽  
Hiv 1

scholarly journals Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations

2018 ◽  
Vol 115 (45) ◽  
pp. 11519-11524 ◽  
Author(s):  
Caitlin M. Quinn ◽  
Mingzhang Wang ◽  
Matthew P. Fritz ◽  
Brent Runge ◽  
Jinwoo Ahn ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Dynamics Simulations ◽  
Building Blocks ◽  
Magic Angle Spinning ◽  
Magic Angle ◽  
Capsid Assembly ◽  
Dynamic Regulation ◽  
Angle Spinning ◽  
Dynamics Simulations ◽  
Hiv 1

The host factor protein TRIM5α plays an important role in restricting the host range of HIV-1, interfering with the integrity of the HIV-1 capsid. TRIM5 triggers an antiviral innate immune response by functioning as a capsid pattern recognition receptor, although the precise mechanism by which the restriction is imposed is not completely understood. Here we used an integrated magic-angle spinning nuclear magnetic resonance and molecular dynamics simulations approach to characterize, at atomic resolution, the dynamics of the capsid’s hexameric and pentameric building blocks, and the interactions with TRIM5α in the assembled capsid. Our data indicate that assemblies in the presence of the pentameric subunits are more rigid on the microsecond to millisecond timescales than tubes containing only hexamers. This feature may be of key importance for controlling the capsid’s morphology and stability. In addition, we found that TRIM5α binding to capsid induces global rigidification and perturbs key intermolecular interfaces essential for higher-order capsid assembly, with structural and dynamic changes occurring throughout the entire CA polypeptide chain in the assembly, rather than being limited to a specific protein-protein interface. Taken together, our results suggest that TRIM5α uses several mechanisms to destabilize the capsid lattice, ultimately inducing its disassembly. Our findings add to a growing body of work indicating that dynamic allostery plays a pivotal role in capsid assembly and HIV-1 infectivity.

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