scholarly journals On the Nature of the Apparent Free Energy of Inserting Amino Acids into Membrane through the Translocon

2013 ◽  
Vol 117 (44) ◽  
pp. 13748-13754 ◽  
Author(s):  
Anna Rychkova ◽  
Arieh Warshel
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Apparent Free Energy

scholarly journals Energetics of side-chain snorkeling in transmembrane helices probed by nonproteinogenic amino acids

2016 ◽  
Vol 113 (38) ◽  
pp. 10559-10564 ◽  
Author(s):  
Karin Öjemalm ◽  
Takashi Higuchi ◽  
Patricia Lara ◽  
Erik Lindahl ◽  
Hiroaki Suga ◽  
...  
Keyword(s):  
Amino Acids ◽  
Membrane Protein ◽  
Side Chain ◽  
Transmembrane Helices ◽  
Transmembrane Segments ◽  
Charged Amino Acids ◽  
Protein Biogenesis ◽  
Quantitative Basis ◽  
Apparent Free Energy ◽  
Integration Efficiency

Cotranslational translocon-mediated insertion of membrane proteins into the endoplasmic reticulum is a key process in membrane protein biogenesis. Although the mechanism is understood in outline, quantitative data on the energetics of the process is scarce. Here, we have measured the effect on membrane integration efficiency of nonproteinogenic analogs of the positively charged amino acids arginine and lysine incorporated into model transmembrane segments. We provide estimates of the influence on the apparent free energy of membrane integration (ΔGapp) of “snorkeling” of charged amino acids toward the lipid–water interface, and of charge neutralization. We further determine the effect of fluorine atoms and backbone hydrogen bonds (H-bonds) on ΔGapp. These results help establish a quantitative basis for our understanding of membrane protein assembly in eukaryotic cells.

Thermodynamics of Helix formation in small peptides of varying lengthin vacuo, implicit solvent and explicit solvent: Comparison between AMBER force fields

2019 ◽  
Vol 18 (03) ◽  
pp. 1950015
Author(s):  
Zhaoxi Sun ◽  
Xiaohui Wang
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Hydrogen Bonds ◽  
Force Fields ◽  
Implicit Solvent ◽  
Conformational Ensemble ◽  
Helix Formation ◽  
Solvent Models ◽  
Explicit Solvent ◽  
Amber Force Fields

Helix formation is of great significance in protein folding. The helix-forming tendencies of amino acids are accumulated along the sequence to determine the helix-forming tendency of peptides. Computer simulation can be used to model this process in atomic details and give structural insights. In the current work, we employ equilibrate-state free energy simulation to systematically study the folding/unfolding thermodynamics of a series of mutated peptides. Two AMBER force fields including AMBER99SB and AMBER14SB are compared. The new 14SB force field uses refitted torsion parameters compared with 99SB and they share the same atomic charge scheme. We find that in vacuo the helix formation is mutation dependent, which reflects the different helix propensities of different amino acids. In general, there are helix formers, helix indifferent groups and helix breakers. The helical structure becomes more favored when the length of the sequence becomes longer, which arises from the formation of additional backbone hydrogen bonds in the lengthened sequence. Therefore, the helix indifferent groups and helix breakers will become helix formers in long sequences. Also, protonation-dependent helix formation is observed for ionizable groups. In 14SB, the helical structures are more stable than in 99SB and differences can be observed in their grouping schemes, especially in the helix indifferent group. In solvents, all mutations are helix indifferent due to protein–solvent interactions. The decrease in the number of backbone hydrogen bonds is the same with the increase in the number of protein–water hydrogen bonds. The 14SB in explicit solvent is able to capture the free energy minima in the helical state while 14SB in implicit solvent, 99SB in explicit solvent and 99SB in implicit solvent cannot. The helix propensities calculated under 14SB agree with the corresponding experimental values, while the 99SB results obviously deviate from the references. Hence, implicit solvent models are unable to correctly describe the thermodynamics even for the simple helix formation in isolated peptides. Well-developed force fields and explicit solvents are needed to correctly describe the protein dynamics. Aside from the free energy, differences in conformational ensemble under different force fields in different solvent models are observed. The numbers of hydrogen bonds formed under different force fields agree and they are mostly determined by the solvent model.

scholarly journals Chirality-Dependent Adsorption between Amphipathic Peptide and POPC Membrane

2019 ◽  
Vol 20 (19) ◽  
pp. 4760
Author(s):  
Ke Chen ◽  
Yuebiao Sheng ◽  
Jun Wang ◽  
Wei Wang
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Umbrella Sampling ◽  
Free Energy Barrier ◽  
Chiral Molecules ◽  
Local Interactions ◽  
Amphipathic Peptide ◽  
Slow Kinetics ◽  
Chiral Amino Acids ◽  
Free Energy Landscapes

The interactions between chiral molecules and cell membranes have attracted more and more attention in recent decades, due to their importance in molecular science and medical applications. It is observed that some peptides composed of different chiral amino acids may have distinct interactions with a membrane. How does the membrane exhibit a selective behavior related to the chirality of the peptides? Microscopically, the interactions between the peptides and the membrane are poorly understood. In this work, we study the interactions between an amphipathic peptide (C6) and POPC membrane with simulations. The kinetics and thermodynamics of peptide enantiomers during the adsorption to the membrane are characterized with direct simulations and umbrella sampling. It is observed that there are slow kinetics for the peptide composed of D-type amino acids. Along the observed pathways, the free energy landscapes are determined with umbrella sampling techniques. A free-energy barrier for the peptide composed of D-amino acids is observed, which is consistent with the kinetic observations. The results indicate the concurrent adsorption and rotation of the peptide helix. The local interactions between the peptides and the membrane are examined in detail, including the contact interactions between the peptides and the membrane, and the distributions of the lipids around the peptide. There are observable differences of the local interactions for the cases related to different peptide enantiomers. These results further demonstrate the importance of the rotation of peptide helix during the adsorption. More interestingly, all these kinetic differences between peptide enantiomers can be explained based on the conformations of the residue Trp and interactions between Trp and lipid molecules. These results give us a molecular understanding of the mechanism of the chirality-dependent peptide–membrane interactions, and may provide clues to designing systems which are sensitive to the chirality of membranes.

Binding Free Energy Calculations of Nine FDA-approved Protease Inhibitors Against HIV-1 Subtype C I36T↑T Containing 100 Amino Acids Per Monomer

2016 ◽  
Vol 87 (4) ◽  
pp. 487-498 ◽  
Author(s):  
Husain A. Lockhat ◽  
José R. A. Silva ◽  
Cláudio N. Alves ◽  
Thavendran Govender ◽  
Jerônimo Lameira ◽  
...  
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Protease Inhibitors ◽  
Binding Free Energy ◽  
Free Energy Calculations ◽  
Subtype C ◽  
Energy Calculations ◽  
Binding Free Energy Calculations ◽  
Hiv 1

Investigation of some amino acids conformations at the interface of binary mixture using the solvation free energy density model

2002 ◽  
Vol 364 (3-4) ◽  
pp. 267-272 ◽  
Author(s):  
Ky-Youb Nam ◽  
Doo Ho Cho ◽  
Kyungsoo Paek ◽  
Kyoung Tai No
Keyword(s):  
Amino Acids ◽  
Free Energy ◽  
Energy Density ◽  
Binary Mixture ◽  
Free Energy Density ◽  
Solvation Free Energy ◽  
Density Model

Exploring the role of ions and amino acids in directing the growth of minerals from solution

2008 ◽  
Vol 72 (1) ◽  
pp. 273-276 ◽  
Author(s):  
S. Piana ◽  
F. Jones ◽  
Z. Taylor ◽  
P. Raiteri ◽  
J. D. Gale
Keyword(s):  
Amino Acids ◽  
Computer Simulation ◽  
Free Energy ◽  
Aspartic Acid ◽  
Morphology Control ◽  
New Approach ◽  
Activation Free Energy

AbstractThe influence of both sulphate ions and aspartic acid on directing the growth of baryte has been explored using computer simulation. Both species are found to significantly reduce the activation free-energy to growth under appropriate conditions, with the influence of sulphate being surface specific. This offers the potential for a new approach to morphology control without inhibition that may have implications for biomineralization.

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