scholarly journals Roles of conserved tryptophans in trimerization of HIV-1 membrane-proximal external regions: Implications for virucidal design via alchemical free-energy molecular simulations

2018 ◽  
Vol 86 (7) ◽  
pp. 707-711 ◽  
Author(s):  
Steven T. Gossert ◽  
Bibek Parajuli ◽  
Irwin Chaiken ◽  
Cameron F. Abrams
Keyword(s):  
Free Energy ◽  
Molecular Simulations ◽  
Alchemical Free Energy ◽  
Hiv 1

scholarly journals Roles of variable linker length in dual acting virucidal entry inhibitors on HIV ‐1 potency via on‐the‐fly free energy molecular simulations

2020 ◽  
Vol 29 (11) ◽  
pp. 2304-2310 ◽  
Author(s):  
Steven T. Gossert ◽  
Bibek Parajuli ◽  
Irwin Chaiken ◽  
Cameron F. Abrams
Keyword(s):  
Free Energy ◽  
Molecular Simulations ◽  
Linker Length ◽  
Entry Inhibitors ◽  
Hiv 1

SAMPL6 Octanol-Water Partition Coefficients from Alchemical Free Energy Calculations with MBIS Atomic Charges

2019 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Free Energy ◽  
Electron Density ◽  
Free Energy Calculations ◽  
Basis Set ◽  
Energetic Cost ◽  
Atomic Charges ◽  
Free Energies ◽  
Energy Calculations ◽  
Alchemical Free Energy ◽  
Alchemical Free Energy Calculations

In molecular modeling the description of the interactions between molecules forms the basis for a correct prediction of macroscopic observables. Here, we derive atomic charges from the implicitly polarized electron density of eleven molecules in the SAMPL6 challenge using the Hirshfeld-I and Minimal Basis Set Iterative Stockholder(MBIS) partitioning method. These atomic charges combined with other parameters in the GAFF force field and different water/octanol models were then used in alchemical free energy calculations to obtain hydration and solvation free energies, which after correction for the polarization cost, result in the blind prediction of the partition coefficient. From the tested partitioning methods and water models the S-MBIS atomic charges with the TIP3P water model presented the smallest deviation from the experiment. Conformational dependence of the free energies and the energetic cost associated with the polarization of the electron density are discussed.

scholarly journals How proteins open fusion pores: insights from molecular simulations

2020 ◽  
Author(s):  
H. Jelger Risselada ◽  
Helmut Grubmüller
Keyword(s):  
Free Energy ◽  
Fusion Proteins ◽  
Graphics Processing Units ◽  
Fusion Reaction ◽  
Molecular Simulations ◽  
Minimum Free Energy ◽  
Free Energy Calculations ◽  
Coarse Grained ◽  
Fusion Pore ◽  
Graphics Processing

AbstractFusion proteins can play a versatile and involved role during all stages of the fusion reaction. Their roles go far beyond forcing the opposing membranes into close proximity to drive stalk formation and fusion. Molecular simulations have played a central role in providing a molecular understanding of how fusion proteins actively overcome the free energy barriers of the fusion reaction up to the expansion of the fusion pore. Unexpectedly, molecular simulations have revealed a preference of the biological fusion reaction to proceed through asymmetric pathways resulting in the formation of, e.g., a stalk-hole complex, rim-pore, or vertex pore. Force-field based molecular simulations are now able to directly resolve the minimum free-energy path in protein-mediated fusion as well as quantifying the free energies of formed reaction intermediates. Ongoing developments in Graphics Processing Units (GPUs), free energy calculations, and coarse-grained force-fields will soon gain additional insights into the diverse roles of fusion proteins.

scholarly journals Free Energy-Based Virtual Screening and Optimization of RNase H Inhibitors of HIV-1 Reverse Transcriptase

ACS Omega ◽  
2016 ◽  
Vol 1 (3) ◽  
pp. 435-447 ◽  
Author(s):  
Baofeng Zhang ◽  
Michael P. D’Erasmo ◽  
Ryan P. Murelli ◽  
Emilio Gallicchio
Keyword(s):  
Free Energy ◽  
Virtual Screening ◽  
Reverse Transcriptase ◽  
Rnase H ◽  
Hiv 1
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