From owner-chemistry@ccl.net Sun Oct 3 11:21:00 2021 From: "Muhammad Shabbir agri_chemist#,#yahoo.com" To: CCL Subject: CCL: Binding free energy from QM/MM Calculation for Ligand Protein complex Message-Id: <-54468-211003110221-25879-BT0yxnfi6IYTDP3nZjZOrw,,server.ccl.net> X-Original-From: "Muhammad Shabbir" Date: Sun, 3 Oct 2021 11:02:13 -0400 Sent to CCL by: "Muhammad Shabbir" [agri_chemist.]^[.yahoo.com] Dear Colleagues,We want to calculate binding free energy of Ligand-Protein complex. After completing QM/MM run we got following energies for complex:----------here Ligand]^[B3LYP/6-31G* and protein]^[UFF=qeq ------------- UFF calculation of energy. Energy= 0.453152500 NIter= 0. Dipole moment= -1.265215 2.913698 -3.244704 ONIOM: saving gridpoint 1 ONIOM: restoring gridpoint 3 ONIOM: calculating energy. ONIOM: gridpoint 1 method: low system: model energy: 0.453152500428 ONIOM: gridpoint 2 method: high system: model energy: -1573.304203057569 ONIOM: gridpoint 3 method: low system: real energy: 23.105333051841 ONIOM: extrapolated energy = -1550.652022506156 ONIOM: calculating electric field derivatives. ONIOM: Integrating ONIOM file 4 number 619 ONIOM: Dipole = 3.51466451D+00 7.85225957D+00 6.59929946D+00 ONIOM: Dipole moment (Debye): X= 8.9334 Y= 19.9585 Z= 16.7737 Tot= 27.5591 ------------------------ My question is how to get binding free energy from these values? or is there need to run ligand and protein separately on QM and MM levels also as in complex?Any information on working equations for QM?MM binding free energy calculation will be greatly appreciated!! Dr.Shabbir From owner-chemistry@ccl.net Sun Oct 3 18:12:01 2021 From: "Igors Mihailovs igorsm(-)cfi.lu.lv" To: CCL Subject: CCL: =?US-ASCII?Q?Re=3A_CCL=3A_Binding_free_energy_from_QM/MM?= =?US-ASCII?Q?_Calculation_for_Ligand_Protein_complex?= Message-Id: <-54469-211003175728-2118-iDwhpjLhhjG4vdjdCiWwBw_+_server.ccl.net> X-Original-From: Igors Mihailovs Content-Transfer-Encoding: 7bit Content-Type: multipart/alternative; boundary=----7BYD3ELSNOQ3NHVS6OENMPPGLZ5DLP Date: Mon, 04 Oct 2021 00:57:14 +0300 MIME-Version: 1.0 Sent to CCL by: Igors Mihailovs [igorsm%a%cfi.lu.lv] ------7BYD3ELSNOQ3NHVS6OENMPPGLZ5DLP Content-Type: text/plain; charset=utf-8 Content-Transfer-Encoding: quoted-printable Dear Dr=2E Shabbir, QM/MM is found in two flavours: additive (or classic) QM/MM and subtractiv= e QM/MM (including ONIOM)=2E In the first case, you have one calculation fo= r Your proteine and one for Your ligand (with different methods, hence You = still cannot actually get the binding energy because there will be no compa= rable energy for the low-level system)=2E In the other case (of ONIOM) You also don't have the low-level system's en= ergy because it is not calculated explicitly at all but just as the part of= the whole system (proteine AND ligand together at the low-level method)=2E Therefore yes, QM/MM is not the right method for calculating the binding e= nergy per se; but You can probably successfully use QM/MM of any kind for 1= ) proteine; 2) ligand; 3) proteine+ligand, and from these three energies Yo= u can get the binding energy (E=3D3-1-2)=2E In fact, the question whether o= ne can use QM/MM for calculating the binding energy is similar to the quest= ion whether one can use Hartree--Fock or B3LYP for calculating the binding = energy, or whether one can use sand for shoveling the cement -- it's just n= ot the right plane of thinking=2E I hope this is helpful=2E Sincerely, IM On 3 October 2021 18:02:13 EEST, "Muhammad Shabbir agri_chemist#,#yahoo=2E= com" wrote: > >Sent to CCL by: "Muhammad Shabbir" [agri_chemist=2E|-|=2Eyahoo=2Ecom] >Dear Colleagues,We want to calculate binding free energy of Ligand-Protei= n complex=2E After completing QM/MM run we got following energies for > > complex:----------here Ligand-$-B3LYP/6-31G* and protein-$-UFF=3Dqeq ---= ----------=20 >UFF calculation of energy=2E >Energy=3D 0=2E453152500 NIter=3D 0=2E >Dipole moment=3D -1=2E265215 2=2E913698 -3=2E244704 >ONIOM: saving gridpoint 1 >ONIOM: restoring gridpoint 3 >ONIOM: calculating energy=2E >ONIOM: gridpoint 1 method: low system: model energy: 0=2E453152500428 >ONIOM: gridpoint 2 method: high system: model energy: -1573=2E30420305756= 9 >ONIOM: gridpoint 3 method: low system: real energy: 23=2E105333051841 >ONIOM: extrapolated energy =3D -1550=2E652022506156 >ONIOM: calculating electric field derivatives=2E >ONIOM: Integrating ONIOM file 4 number 619 >ONIOM: Dipole =3D 3=2E51466451D+00 7=2E85225957D+00 6=2E59929946D+00 >ONIOM: Dipole moment (Debye): > X=3D 8=2E9334 Y=3D 19=2E9585 Z=3D 16=2E7737 Tot=3D 27=2E5591 >------------------------ > >My question is how to get binding free energy from these values? or is th= ere need to run ligand and protein separately on QM and MM levels also as i= n complex?Any information on working equations for QM?MM binding free energ= y calculation will be greatly appreciated!! >Dr=2EShabbir > > > >-=3D This is automatically added to each message by the mailing script = =3D->the strange characters on the top line to the |-| sign=2E You can also >look up the X-Original-From: line in the mail header=2E > >E-mail to subscribers: CHEMISTRY|-|ccl=2Enet or use: > http://www=2Eccl=2Enet/cgi-bin/ccl/send_ccl_message > >E-mail to administrators: CHEMISTRY-REQUEST|-|ccl=2Enet or use > http://www=2Eccl=2Enet/cgi-bin/ccl/send_ccl_message > >Subscribe/Unsubscribe:=20 > http://www=2Eccl=2Enet/chemistry/sub_unsub=2Eshtml > >Before posting, check wait time at: http://www=2Eccl=2Enet > >Job: http://www=2Eccl=2Enet/jobs=20 >Conferences: http://server=2Eccl=2Enet/chemistry/announcements/conference= s/ > >Search Messages: http://www=2Eccl=2Enet/chemistry/searchccl/index=2Eshtml > >If your mail bounces from CCL with 5=2E7=2E1 error, check: > http://www=2Eccl=2Enet/spammers=2Etxt > >RTFI: http://www=2Eccl=2Enet/chemistry/aboutccl/instructions/ > > --=20 Sent from my Android device with K-9 Mail=2E Please excuse my brevity=2E ------7BYD3ELSNOQ3NHVS6OENMPPGLZ5DLP Content-Type: text/html; charset=utf-8 Content-Transfer-Encoding: quoted-printable Dear Dr=2E Shabbir,

QM/MM is found in two f= lavours: additive (or classic) QM/MM and subtractive QM/MM (including ONIOM= )=2E In the first case, you have one calculation for Your proteine and one = for Your ligand (with different methods, hence You still cannot actually ge= t the binding energy because there will be no comparable energy for the low= -level system)=2E
In the other case (of ONIOM) You also don't have the l= ow-level system's energy because it is not calculated explicitly at all but= just as the part of the whole system (proteine AND ligand together at the = low-level method)=2E

Therefore yes, QM/MM is not the right method fo= r calculating the binding energy per se; but You can probably successfully = use QM/MM of any kind for 1) proteine; 2) ligand; 3) proteine+ligand, and f= rom these three energies You can get the binding energy (E=3D3-1-2)=2E In f= act, the question whether one can use QM/MM for calculating the binding ene= rgy is similar to the question whether one can use Hartree--Fock or B3LYP f= or calculating the binding energy, or whether one can use sand for shovelin= g the cement -- it's just not the right plane of thinking=2E

I hope = this is helpful=2E

Sincerely,
IM

On 3 October 2021 18:02:13 EEST, "Muhammad Shabbir agri_chemist#,#yahoo= =2Ecom" <owner-chemistry|-|ccl=2Enet> wrote:

Sent to CCL by: "Muhammad  Shabbir"=
 [agri_chemist=2E|-|=2Eyahoo=2Ecom]
Dear Colleagues,We want to calculate b=
inding free energy of Ligand-Protein complex=2E After completing QM/MM run =
we got following energies for

 complex:----------here Ligand-$-B3LYP=
/6-31G* and protein-$-UFF=3Dqeq ------------- 
UFF calculation of energy=
=2E
Energy=3D  0=2E453152500   NIter=3D  0=2E
Dipole moment=3D   -1=
=2E265215    2=2E913698   -3=2E244704
ONIOM: saving gridpoint 1
ONIOM=
: restoring gridpoint 3
ONIOM: calculating energy=2E
ONIOM: gridpoint=
 1 method: low  system: model energy:   0=2E453152500428
ONIOM: gridpoin=
t 2 method: high system: model energy: -1573=2E304203057569
ONIOM: gridp=
oint 3 method: low  system: real energy:  23=2E105333051841
ONIOM: extra=
polated energy =3D  -1550=2E652022506156
ONIOM: calculating electric fie=
ld derivatives=2E
ONIOM: Integrating ONIOM file 4 number  619
ONIOM: =
Dipole    =3D 3=2E51466451D+00 7=2E85225957D+00 6=2E59929946D+00
ONIOM: =
Dipole moment (Debye):
  X=3D   8=2E9334  Y=3D  19=2E9585  Z=3D  16=2E77=
37 Tot=3D  27=2E5591
My question is how to get binding free energy from =
these values? or is there need to run ligand and protein separately on QM a=
nd MM levels also as in complex?Any information on working equations for QM=
?MM binding free energy calculation will be greatly appreciated!!
Dr=2ES=
habbir



-=3D This is automatically added to each message by t=
he mailing script =3D-
To recover the email address of the author of the=
 message, please change
the strange characters on the top line to the |-| =
sign=2E You can also
look up the X-Original-From: line in the mail heade=
r=2E

E-mail to subscribers: CHEMISTRY|-|ccl=2Enet or use:
      http://www=2Ec=
cl=2Enet/cgi-bin/ccl/send_ccl_message

E-mail to administrators: =
CHEMISTRY-REQUEST|-|ccl=2Enet or use
      http://www=2Eccl=2Enet/cgi-bin/ccl/send_cc=
l_message
      http://www=2Eccl=2Enet/chemistry/=
sub_unsub=2Eshtml

Before posting, check wait time at: http://www=2Eccl=2Enet

Job: http://www=2Eccl=2Enet/jobs 
Conference=
s: http://server=2Eccl=2Enet/chemistry/announcements/conferences/
Search Messages: http://www=2Eccl=2Enet/chemistry/searchccl/index=2Eshtml
If your mail bounces from CCL with 5=2E7=2E1 error, check:
      <=
a href=3D"http://www=2Eccl=2Enet/spammers=2Etxt">http://www=2Eccl=2Enet/spa=
mmers=2Etxt

RTFI: http://www=2Eccl=2Enet/chemistry/aboutccl/instruction=
s/


--
Sent from my Android device wit= h K-9 Mail=2E Please excuse my brevity=2E
------7BYD3ELSNOQ3NHVS6OENMPPGLZ5DLP--