+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Determination of membrane-insertion free energies by molecular dynamics simulations



Determination of membrane-insertion free energies by molecular dynamics simulations



Biophysical Journal 102(4): 795-801



The accurate prediction of membrane-insertion probability for arbitrary protein sequences is a critical challenge to identifying membrane proteins and determining their folded structures. Although algorithms based on sequence statistics have had moderate success, a complete understanding of the energetic factors that drive the insertion of membrane proteins is essential to thoroughly meeting this challenge. In the last few years, numerous attempts to define a free-energy scale for amino-acid insertion have been made, yet disagreement between most experimental and theoretical scales persists. However, for a recently resolved water-to-bilayer scale, it is found that molecular dynamics simulations that carefully mimic the conditions of the experiment can reproduce experimental free energies, even when using the same force field as previous computational studies that were cited as evidence of this disagreement. Therefore, it is suggested that experimental and simulation-based scales can both be accurate and that discrepancies stem from disparities in the microscopic processes being considered rather than methodological errors. Furthermore, these disparities make the development of a single universally applicable membrane-insertion free energy scale difficult.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 052532965

Download citation: RISBibTeXText

PMID: 22385850

DOI: 10.1016/j.bpj.2012.01.021


Related references

Determination of Ionic Hydration Free Energies with Grand Canonical Monte Carlo/Molecular Dynamics Simulations in Explicit Water. Journal of Chemical Theory and Computation 14(10): 5290-5302, 2018

Computations of standard binding free energies with molecular dynamics simulations. Journal of Physical Chemistry. B 113(8): 2234-2246, 2009

Predictions of hydration free energies from all-atom molecular dynamics simulations. Journal of Physical Chemistry. B 113(14): 4533-4537, 2009

Efficient calculation of many stacking and pairing free energies in DNA from a few molecular dynamics simulations. Chemistry 11(15): 4340-4348, 2005

Free energies of point defects in sodium from first-principles molecular-dynamics simulations. Physical Review. B Condensed Matter 51(1): 129-136, 1995

Estimation of binding free energies for HIV proteinase inhibitors by molecular dynamics simulations. Protein Engineering 8(11): 1137-1144, 1995

LAMBADA and InflateGRO2: efficient membrane alignment and insertion of membrane proteins for molecular dynamics simulations. Journal of Chemical Information and Modeling 52(10): 2657-2669, 2012

Absolute free energies of binding of peptide analogs to the HIV-1 protease from molecular dynamics simulations. Journal of Computational Chemistry 26(12): 1294-1305, 2005

Interaction of amino acids with the Au(111) surface: adsorption free energies from molecular dynamics simulations. Langmuir 26(11): 8347-8351, 2010

Step free energies at faceted solid-liquid interfaces from equilibrium molecular dynamics simulations. Journal of Chemical Physics 137(21): 214108, 2012

Predicting hydration free energies using all-atom molecular dynamics simulations and multiple starting conformations. Journal of Computer-Aided Molecular Design 24(4): 307-316, 2010

Hydration free energies of cyanide and hydroxide ions from molecular dynamics simulations with accurate force fields. Physical Chemistry Chemical Physics 15(46): 20303-20312, 2013

CXC and CC chemokines form mixed heterodimers: association free energies from molecular dynamics simulations and experimental correlations. Journal of Biological Chemistry 283(35): 24155-24166, 2008

Molecular dynamics simulations of 2-amino-6-arylsulphonylbenzonitriles analogues as HIV inhibitors: interaction modes and binding free energies. Chemical Biology and Drug Design 76(6): 518-526, 2010

Free energies of absorption of alkali ions onto beidellite and montmorillonite surfaces from constrained molecular dynamics simulations. Geochimica et Cosmochimica Acta 91(none), 2012