scholarly journals Unexpected trends in the hydrophobicity of fluorinated amino acids reflect competing changes in polarity and conformation

2019 ◽  
Vol 21 (4) ◽  
pp. 2029-2038 ◽  
Author(s):  
João R. Robalo ◽  
Ana Vila Verde
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Analytical Model ◽  
Molecular Simulations ◽  
Hydration Free Energy ◽  
Fluorinated Amino Acids

The hydration free energy of fluorinated amino acids is calculated with molecular simulations and explained with an analytical model.

scholarly journals Unexpected Trends in the Hydrophobicity of Fluorinated Amino Acids Reflect Competing Changes in Polarity and Conformation

2018 ◽  
Author(s):  
João R. Robalo ◽  
Ana Vila Verde
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Side Chain ◽  
Side Chains ◽  
Hydration Free Energy ◽  
Crossover Point ◽  
Fluorinated Amino Acids ◽  
Road Map ◽  
Alkyl Side Chains ◽  
The Impact

<div><div><div><p>Fluorination can dramatically improve the thermal and proteolytic stability of proteins and their enzymatic activity. Key to the impact of fluorination on protein properties is the hydrophobicity of fluorinated amino acids. We use molecular dynamics simulations, together with a new fixed-charge, atomistic force field, to quantify the changes in hydration free energy for amino acids with alkyl side chains and with 1 to 6 –CH to –CF side chain substitutions. Fluorination changes the hydration free energy by 1.5 to +2 kcal mol<sup>-</sup>1, but the number of fluorines is a poor predictor of hydrophobicity. Changes in hydration free energy reflect two main contributions: i) fluorination alters side chain-water interactions; we identify a crossover point from hydrophilic to hydrophobic fluoromethyl groups which may be used to estimate the hydrophobicity of fluorinated alkyl side-chains; ii) fluorination alters the number of backbone-water hydrogen bonds via changes in the relative side chain-backbone conformation. Our results offer a road map to mechanistically understand how fluorination alters hydrophobicity of (bio)polymers.</p></div></div></div>

scholarly journals Unexpected Trends in the Hydrophobicity of Fluorinated Amino Acids Reflect Competing Changes in Polarity and Conformation

2018 ◽  
Author(s):  
João R. Robalo ◽  
Ana Vila Verde
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Side Chain ◽  
Side Chains ◽  
Hydration Free Energy ◽  
Crossover Point ◽  
Fluorinated Amino Acids ◽  
Road Map ◽  
Alkyl Side Chains ◽  
The Impact

<div><div><div><p>Fluorination can dramatically improve the thermal and proteolytic stability of proteins and their enzymatic activity. Key to the impact of fluorination on protein properties is the hydrophobicity of fluorinated amino acids. We use molecular dynamics simulations, together with a new fixed-charge, atomistic force field, to quantify the changes in hydration free energy for amino acids with alkyl side chains and with 1 to 6 –CH to –CF side chain substitutions. Fluorination changes the hydration free energy by 1.5 to +2 kcal mol<sup>-</sup>1, but the number of fluorines is a poor predictor of hydrophobicity. Changes in hydration free energy reflect two main contributions: i) fluorination alters side chain-water interactions; we identify a crossover point from hydrophilic to hydrophobic fluoromethyl groups which may be used to estimate the hydrophobicity of fluorinated alkyl side-chains; ii) fluorination alters the number of backbone-water hydrogen bonds via changes in the relative side chain-backbone conformation. Our results offer a road map to mechanistically understand how fluorination alters hydrophobicity of (bio)polymers.</p></div></div></div>

On the transferability of fractional contributions to the hydration free energy of amino acids

2013 ◽  
Vol 132 (3) ◽  
Author(s):  
Josep M. Campanera ◽  
Xavier Barril ◽  
F. Javier Luque
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Hydration Free Energy

Free energy of conformational change in a single chain of polyvinylidene fluoride using molecular simulations

2021 ◽  
Vol 61 (4) ◽  
pp. 1270-1280
Author(s):  
Shubham Mireja ◽  
Devang V. Khakhar
Keyword(s):  
Free Energy ◽  
Conformational Change ◽  
Polyvinylidene Fluoride ◽  
Molecular Simulations ◽  
Single Chain

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.

Sign in / Sign up

Export Citation Format

Share Document