scholarly journals Identifying binding hot spots on protein surfaces by mixed-solvent molecular dynamics: HIV-1 protease as a test case

Biopolymers ◽  
2015 ◽  
Vol 105 (1) ◽  
pp. 21-34 ◽  
Author(s):  
Peter M. U. Ung ◽  
Phani Ghanakota ◽  
Sarah E. Graham ◽  
Katrina W. Lexa ◽  
Heather A. Carlson
Keyword(s):  
Molecular Dynamics ◽  
Hot Spots ◽  
Mixed Solvent ◽  
Test Case ◽  
Protein Surfaces ◽  
Hiv 1

Molecular Docking and Molecular Dynamics Simulation Based Approach to Explore the Dual Inhibitor Against HIV-1 Reverse Transcriptase and Integrase

2017 ◽  
Vol 20 (8) ◽  
Author(s):  
Subhash Chander ◽  
Rajan Kumar Pandey ◽  
Ashok Penta ◽  
Bhanwar Singh Choudhary ◽  
Manish Sharma ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Molecular Dynamics Simulation ◽  
Reverse Transcriptase ◽  
Dynamics Simulation ◽  
Dual Inhibitor ◽  
Simulation Based ◽  
Hiv 1

Ordered Water and Ligand Mobility in the HIV-1 Integrase-5CITEP Complex:  A Molecular Dynamics Study

2001 ◽  
Vol 44 (19) ◽  
pp. 3043-3047 ◽  
Author(s):  
Ni ◽  
Christoph A. Sotriffer ◽  
J. Andrew McCammon
Keyword(s):  
Molecular Dynamics ◽  
Ordered Water ◽  
Hiv 1

scholarly journals Activities, Crystal Structures, and Molecular Dynamics of Dihydro-1H-isoindole Derivatives, Inhibitors of HIV-1 Integrase

2012 ◽  
Vol 8 (1) ◽  
pp. 209-217 ◽  
Author(s):  
Mathieu Métifiot ◽  
Kasthuraiah Maddali ◽  
Barry C. Johnson ◽  
Stephen Hare ◽  
Steven J. Smith ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Crystal Structures ◽  
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

Investigating potency of TMC-126 against wild-type and mutant variants of HIV-1 protease: a molecular dynamics and free energy study

2021 ◽  
Vol 32 (11) ◽  
pp. 941-962
Author(s):  
M.F. Sk ◽  
S. Haridev ◽  
R. Roy ◽  
P. Kar
Keyword(s):  
Molecular Dynamics ◽  
Free Energy ◽  
Wild Type ◽  
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.

scholarly journals Nature, Position, and Frequency of Mutations Made in a Single Cycle of HIV-1 Replication

2010 ◽  
Vol 84 (19) ◽  
pp. 9864-9878 ◽  
Author(s):  
Michael E. Abram ◽  
Andrea L. Ferris ◽  
Wei Shao ◽  
W. Gregory Alvord ◽  
Stephen H. Hughes
Keyword(s):  
Viral Replication ◽  
Mutation Rate ◽  
Hot Spots ◽  
High Rate ◽  
Published Data ◽  
Single Cycle ◽  
Efficient System ◽  
Hiv 1

ABSTRACT There is considerable HIV-1 variation in patients. The extent of the variation is due to the high rate of viral replication, the high viral load, and the errors made during viral replication. Mutations can arise from errors made either by host DNA-dependent RNA polymerase II or by HIV-1 reverse transcriptase (RT), but the relative contributions of these two enzymes to the mutation rate are unknown. In addition, mutations in RT can affect its fidelity, but the effect of mutations in RT on the nature of the mutations that arise in vivo is poorly understood. We have developed an efficient system, based on existing technology, to analyze the mutations that arise in an HIV-1 vector in a single cycle of replication. A lacZα reporter gene is used to identify viral DNAs that contain mutations which are analyzed by DNA sequencing. The forward mutation rate in this system is 1.4 × 10−5 mutations/bp/cycle, equivalent to the retroviral average. This rate is about 3-fold lower than previously reported for HIV-1 in vivo and is much lower than what has been reported for purified HIV-1 RT in vitro. Although the mutation rate was not affected by the orientation of lacZα, the sites favored for mutations (hot spots) in lacZα depended on which strand of lacZα was present in the viral RNA. The pattern of hot spots seen in lacZα in vivo did not match any of the published data obtained when purified RT was used to copy lacZα in vitro.

RNA unrestrained molecular dynamics ensemble improves agreement with experimental NMR data compared to single static structure: a test case

2006 ◽  
Vol 20 (5) ◽  
pp. 263-279 ◽  
Author(s):  
Robert A. Beckman ◽  
David Moreland ◽  
Shirley Louise-May ◽  
Christine Humblet
Keyword(s):  
Molecular Dynamics ◽  
Test Case ◽  
Static Structure ◽  
Nmr Data
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