Admin: Created page with "= Introduction
= == What is QM/MM?
== Hybrid method that QM (Quantum mechanics) and MM (molecular mechanics) calculation schemes The system is divided into two regions QM and MM regions Regions are designed based on compromise in calculation time and accuracy == Why use QM/MM?
== The system is too large to use ''ab initio'' calculations
MM calculations do not give the "correct" answer *Processes involving change in electronic structure..."

2022-05-10T15:52:56Z

Created page with "= Introduction = == What is QM/MM? == *Hybrid method that QM (Quantum mechanics) and MM (molecular mechanics) calculation schemes *The system is divided into two regions **QM and MM regions **Regions are designed based on compromise in calculation time and accuracy == Why use QM/MM? == *The system is too large to use ''ab initio'' calculations *MM calculations do not give the "correct" answer *Processes involving change in electronic structure..."

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= Introduction =

== What is QM/MM? ==

*Hybrid method that QM (Quantum mechanics) and MM (molecular mechanics) calculation schemes
*The system is divided into two regions
**QM and MM regions
**Regions are designed based on compromise in calculation time and accuracy

== Why use QM/MM? ==

*The system is too large to use ''ab initio'' calculations 
*MM calculations do not give the "correct" answer
*Processes involving change in electronic structure

== How QM/MM methods differ?<ref>Eduardo M. Sproviero et all. Photosynth Res. In Press.</ref> ==

=== Treatment of the junction between QM and MM regions ===

==== Use of link atoms ====

*Hydrogen is “inserted” along the bond contained in the QM/MM junction 
**Placed closed to the MM atom 
**Behavior is changed based on the identity of the MM atom 

==== Localized orbitals ====

*Specially designed local orbitals assigned to boundary QM and MM atoms<ref name="Hu">H. Hu, W. Yang / Journal of Molecular Structure: THEOCHEM 898 (2009) 17–30</ref> 
**maintain closure of QM system
**local orbitals are designed and tested based on empirical data
**no need for extra atoms

==== Pseudopotential methods ====

*MM-bounded boundary QM atoms are assigned a special basis set and potential<ref name="Hu" />
**mimic correct covalent bonding scheme
**designed from small system models
**no need for extra atoms

=== Methods of energy calculations ===

==== Subtraction Scheme ====

===== ONIOM - (our own n-layered integrated molecular orbital and molecular mechanics) =====

Method developed by Morokuma and co-workers which allows for different regions of a system to be calculated at different levels of theory and combine to produce a consistent energy expression. <ref name="Morokuma">M. Svensson, S. Humbel, R.D.J. Froese, T. Mastubara, S. Sieber, and K. Morokuma, J.Phys.Chem., 100, 19357 (1996).</ref>

[[Image:Oniom.png|704x208px]]

E(ONIOM2) = E(High, region 1) + E(low, regions 1 and 2) – E(low, region1) E(ONIOM3) = E(High, region A) +E(Medium, regions A and B) + E(Low, regions A, B and C) – E(Medium, region A) – E(Low, region A and B) [http://www.gaussian.com/g_tech/g_ur/k_oniom.htm www.gaussian.com/g_tech/g_ur/k_oniom.htm]

 

==== Summation scheme ====

Example:

[[Image:2 layer system.png|279x169px]] 

Etotal(1 and 2) = EQM(1 and 2) + EQM/MM, ele(1 and 2) + EQM/MM,nucl(1 and 2) + EQM/MM,vdw(1 and 2) + EQM/MM,covalent(1 and 2) + EMM(2)<ref name="Hu" /> 

=== The way in which the electrostatic interaction between the QM and MM regions are described ===

==== Mechanical embedding ====

Polarization from MM electrostatics comes from interpolation scheme used to combine energy terms.  

==== Electronic embedding ====

QM polarization form MM electrostatics is explicitly considered.

==== Linear-scaled Eward Method ====

Particle-mesh Eward technique with periodic boundary conditions<ref name="Senn">H. M. Senn, W. Thiel. Current Opinion in Chemical Biology 2007, 11:182–187</ref> 

==== GSBP - generalized solvent boundary potential ====

Small region of the system surround QM region is treated explicitly. The remainder of the system is fixed and described in terms of solvent-shielded static field and a Poisson–Boltzmann reaction field.<ref name="Senn" /> 

= Case study =

== Project Introduction ==

=== Goals ===

*Simulate the 1H and 205Tl NMR spectra based MM and QM/MM refined x-ray crystallographic and NMR structures
*Understand how differences in the structure lead to different chemical shifts
*Gain insight into molecular structural information directly from experimental chemical shifts

=== The G-quardruplex Model System ===

[[Image:Gquart.png|250x306px]]                                   [[Image:Guartet.png|251x267px]]

*Model System for the development of 205Tl NMR
**All classes of biomacromolecules bind monovalent cations
**Na+ and K+ are poor spectroscopic nuclei
**Tl+ is an excellent mimic of K+
**205Tl+ is a spin ½ nucleus with a large gyromagnetic ratio
***1H > 19F > 205Tl > 31P
*G4T4G4 is the telomeric sequence from the ciliate Oxytricha Nova
**Homodimeric G-quadruplex with diagonal loops
**Contains four G-quartets, each composed of four guanine bases
**Exceptionally stable and structures have been solved by NMR and X-ray crystallography
**Binds 3-5 monovalent cations 

=== Experimental NMR Spectra <ref name="Gill">Michelle L. Gill, Scott A. Strobel and J. Patrick Loria Am. Chem. Soc. 127, 16723-16732 (2005)</ref> ===

[[Image:Nmr.png|819x490px]]

=== Quantum Mechanics / Molecular Mechanics (QM/MM) Hybrid Methodology<ref name="Gascon 2004">J.A. Gascon and V.S. Batista, Biophys. J. 87, 2931-2941 (2004)</ref><ref name="Gascon 2005">J.A. Gascon, E.M. Sproviero and V.S. Batista, J. Chem. Theor. Comput. 2, 11-20 (2005)</ref> ===

[[Image:Qmmm method.png|690x350px]]

[http://www.gaussian.com/g_tech/g_ur/k_nmr.htm www.gaussian.com/g_tech/g_ur/k_nmr.htm]

[http://www.gaussian.com/g_tech/g_ur/k_oniom.htm www.gaussian.com/g_tech/g_ur/k_oniom.htm]

== 1H NMR simulations ==

[[Image:Proton_nmr_simulation.png|806x509px]]

== 205Tl simulations ==

[[Image:Tl_nmr_simulations.png|903x532px]]

== 205Tl benchmarks<ref>J. Hinton. (1992) Ann Rep NMR Spectr 13, 211</ref> ==

[[Image:Tl_benchmarchs.png|917x528px]]

== 15N simulation of NH4+ bound G-quadruplex<ref>Juli Feigen et al (2001) Methods in Enzymology Vol 338,400</ref> ==

[[Image:Nh4_nmr_simulations.png|968x567px]]

== Case study conclusions ==

*We have completed NMR simulations of G-quadruplet at the QM/MM level where the influence of the surrounding environment is explicitly considered
*1H-NMR is found to be extremely sensitive to the configuration of the system, useful for gaining structural insight
*Stacking greatly impacts the1H NMR Spectra
*The ions most exposed to the loops have different magnetic environments most likely due to structural disorder
*All-electron (UGBS) simulations of 205Tl NMR spectra provide valuable insight on the origin of chemical shifts 

= Further Reading =

H. Hu, W. Yang / Journal of Molecular Structure: THEOCHEM 898 (2009) 17–30 [[Image:H Hu papper 2009.pdf]]

H. M. Senn, W. Thiel. Current Opinion in Chemical Biology 2007, 11:182–187 [[Image:Senn paper.pdf]]

M. Svensson, S. Humbel, R.D.J. Froese, T. Mastubara, S. Sieber, and K. Morokuma, J.Phys.Chem., 100, 19357 (1996). [[Image:Svensson paper.pdf]]

R. A. Friesner and V. Guallar, Annu. Rev. Phys. Chem. 2005. 56:389–427 [[Image:Friesner.pdf ]]

= References =

<references />

Ammm:QM/MM - Revision history