Several problems in free energy calculation

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Several problems in free energy calculation Institute of Biophysics Hebei University of Technology JI Qing 河河河河河河 河河河河河河河 July 2013, Beijing

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Several problems in free energy calculation. JI Qing. 河北工业大学 生物物理研究所. Institute of Biophysics Hebei University of Technology. July 2013, Beijing. 1. Free energy change for kinesin’s neck linker docking. Force generation vs neck linker docking. - PowerPoint PPT Presentation

Transcript of Several problems in free energy calculation

Page 1: Several problems in free energy calculation

Several problems in free energy calculation

Institute of Biophysics

Hebei University of Technology

JI Qing

河北工业大学 生物物理研究所

July 2013, Beijing

Page 2: Several problems in free energy calculation

1. Free energy change for kinesin’s neck linker docking

R.Vale & R.Milligan, Science, 2000.

Force generation vs neck linker docking

Rice et al., Biophysical Journal, 2003

3 /G kJ mol

Method: EPR, spin marker

lnG RT K

K = mobile + intermediate probes

immobilized probes

Too small !

Hackney, PNAS, 2005

Free energy change for NL docking

ATP hydrolysis:

55 /G kJ mol

6 8

28.8 /

W pN nm

kJ mol

Work:

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What’s the problem?

Rice et al., Nature, 1999

extra turn

0

0

9

CNBCover-neck-bundle (CNB) = 0 + neck linker (9)

Hwang et al., Structure, 2008

The problem arises from the understanding of the neck linker docking mechanism.

Neck linker (~ 14 AA) consists of three parts: extra turn, 9 and 10.

Neck linker docking consists of three steps:

(1) Extra turn formation,

(2) 9 docking,

(3) 10 docking.

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2. System-environment interaction vs free energy calculation

Jarzynski’s equality (JE) : W Fe e Jarzynski, PRL, 1997

(1) Single-molecule measurement (2) Steered molecular dynamics simulation

Liphardt et al., Science, 2002 Park et al., JCP, 2003

in solution in vacuum

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Weak coupling assumption ?

JE is valid for sufficiently weak coupling between the system and reservoir. Neglecting Hint

The fluctuations in the work W must not be much greater than kBT. This condition pretty much rules out macroscopic systems of interest.

1 (298.15 ) 2.4789 /Bk T K kJ mol

ATP hydrolysis: 55 /G kJ mol

6 8 28.8 /W pN nm kJ mol Work by kinesin :

H-bond energy: 20 /HE kJ mol

11.72 /F kJ mol

Je-Luen Li, Roberto Car, Chao Tang, and Ned S. Wingreen, PNAS, 2007

The free energy change for the hydrophobic binding of two methane molecules (CH4) in water :

Jarzynski, PRL, 1997

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3. Water system: hydrogen bond identification

“r- ” criterion : 1.59 Å < rO…H < 2.27 Å, > 140°

Pan et al., JCP, 2012

Kuo et al., Science, 2007

Geometric criterion for H bond:

Electronic orbitals of water dimerF E T S

H-H radial distribution function for bulk water

Soper, Chem. Phys., 2000repulsion

E hydrogen bonds

Energy criterion for H bond: 10 /E kJ mol

Number of H bond

“r- ” criterion

Energy criterion

1000 water pairs

701

528

CPMD method, 64 water molecules

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Summary

1. The understanding of the system operating mechanism might affect the experiment design and calculation of free energy.

2. When Hint is comparable with Hsystem, can I directly use Jarzynski’s equality?

3. Water is the most important environment in our world. Water molecule is one of the most important biomolecules. The statistical description of the macroscopic behavior of water must be based on the quantitative knowledge of the microscopic structure and interaction of water molecules. The quantitative calculation of the free energy of water system is still a difficult task.

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Acknowledgement

吕 刚( Gang Lv)张 辉( Hui Zhang )张 博( Bo Zhang )张秀欣( Xiu-Xin Zhang )潘 章( Zhang Pan )耿轶钊( Yi-Zhao Geng )李 铁( Tie Li )覃静宇( Jing-Yu Qin )刘书霞( Shu-Xia Liu )柳睿殊( Rui-Shu Liu )

The National Natural Science Foundation of China , No. 90403007

The National Natural Science Foundation of China , No. 10975044

My students :卓益忠( Yin-Zhong Zhuo)

包景东( Jing-Dong Bao)

张红雨( Hong-Yu Zhang)

晏世伟( Shi-Wei Yan)

My friends and collaborators :