hydration free energy profiles of amino acid side chains at water-air interface lomonosov moscow...
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Hydration Free Energy Profiles of Amino Acid Side Chains at Water-Air Interface
Lomonosov Moscow State UniversityFaculty of Biology
Department of Bioengineering
Alexey Shaytan
MSU
• founded 1755• 39 faculties and 15 research institutions•~35 000 students•~5 000 PHD students•~10 000 research and faculty staff
Molecular Simulations Group
Head – Prof. Konstantin V. Shaitan
Associate Prof. – Nikolai K. Balabaev
Research Staff
Mikhail Antonov Alexey Shaytan Valeriy Novoselezkii
PHD students
Students Marina Kasimova, Olesya Volokh, Mikhail Vishnepolskii
Ann Popinako
TatiyanaNaumenkova
MarineBozdaganyan
PhilippOrekhov
Outline
•) Free energies in MD simulations
•) hydration free energies of amino acids
•) validity of forcefields
•) hydration of molecules at water/air interface
•) free energy profiles
•) adsorption free energies
Free energies and MD simulations
Free energy refers to the amount of work that can be extracted from a system.
F=E-TS
F=-kT lnZ
The
rmod
ynam
ics
Sta
tistic
al p
hysi
cs H(p1,…,pN,x1,…,xN)
Probability~const*exp(-H/kT)
Free energy governs the probability
Protein-ligand binding
Biological system are in water
F=E-TS
Hydrophopic hydration:1)energetically favorable2)Entropically unfavorable
Common protein force fields
, , , , , ,
( ) ( ) ( ) ( ) [ ( ) ( )]b b b c vdwij ij ijk ijk ijkl ijkl ij ij ij ij
i j i j k i j k l i j
U r U b U U U r U r
•CHARMM•AMBER•OPLS•GROMOS
•TIP3P•SPC•SPC/E•TIP4P•TIP5P
Parameterization: an initio + bulk properties + energetical properties
Hydration free energy
Fhydr – hydration free energyWater
Air
Fhydr =-kTln(c1/c2)
Fhydr – free energy of coupling one solute molecule into the rest of solution
“computational alchemistry methods”
Free energy calculations
FEP
TI
BAR
JE
Amino acid R-H-analogs
Conformational simplicity is important
Hydration free energies (R-H-analogs)
FF: OPLS-AA + SPC.
R=0.997Overest. 0-4 kJ/mol
Hydration at interface
Solvent accessible surface of a protein
Fads – adsorption free energy
Water
Air
Fads =-kTln(ca/c2)
Hyd
roph
obic
ity s
cale
Water-air interfaceS
olut
e co
ncen
trat
ion
C(z)C1C2
W(z)=-kTln(C(z)) – free energy profile (PMF)
Fhydr=-kTln(C2/C1) – hydration free energy
Constraint force algorithm
Water-interface system
Water-interface system
surface potential drop is −0.59 V
Profiles
Hydration free energies
Adsorption energies
-Gibbs excess
Adsorption energies
Adsorption energies
Experimental comparison
Bull & Breese (1974) - adsorption energy scale for amino acids side chainsCorrelation is R=0.65
Experiment, kJ/mol Simulation, kJ/mol
Methanol -15.2 -19.2
Experiment, 10^-10 mol/cm^-2 Simulation, 10^-10 mol/cm^-2
Methanol 2.5 1.2
Ethanol 3-5 2.6
Fhydr~Fbb+FR
Fads≠Fbb+FR
Summary
A.K. Shaytan, V.A. Ivanov, K.V. Shaitan , A.R. Khokhlov "Free energy profiles of amino acid side chain analogs near water-vapor interface obtained via MD simulations", // Journal of Computational Chemistry, 2010, 31(1), pp 204-216, DOI:10.1002/jcc.21267
•) We developed a rigorous methodology of estimating adsorption free energies at liquid/gas interface
•) We statistically described the hydration process of small molecules as water/vapor interface
•) Adsorption energies can be used for quality assessment and tuning of molecular forcefields
Thank you for attention!