For decharge, the code checks if the coordinates of the atoms are exactly the same (well if they're within 0.1 angstroms distance apart), so if its finding mismatches in the atom's it means the coordinates of ligand 1 and ligand 2 are different. You need to make sure the ligands have the exact same coordinates.
For vdw, I actually don't have an idea what's going on there. Your input looks correct. Check if for some reason all your residues are named BG1.
On 10/17/19, 7:19 AM, "Sadaf Rani" <sadafrani6.gmail.com> wrote:
CAUTION: EXTERNAL EMAIL
thank you, Charles.
I am facing few problems while running calculations could you please
suggest where I am doing wrong?
I followed protocol as below:-
I used libraries for the charged and uncharged state of ligand to build a
combined PDB file as mentioned in linear scaling, after parametrization and
running a short MD, I followed descharging step as below:-
heating
&cntrl
imin = 0, nstlim = 10000, irest = 0, ntx = 1, dt = 0.002,
ntt = 1, temp0 = 300.0, tempi = 50.0, tautp = 1.0,
ntc = 2, ntf = 1,
ntb = 1,
ioutfm = 1, iwrap = 1,
ntwe = 1000, ntwx = 1000, ntpr = 1000, ntwr = 5000,
nmropt = 1,
ntr = 1, restraint_wt = 5.00,
restraintmask='!:WAT & !.H=',
icfe = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
logdvdl = 0,
timask1 = ':BG0', timask2 = ':BG1',
ifsc = 0,
/
&ewald
/
&wt
type='TEMP0',
istep1 = 0, istep2 = 8000,
value1 = 50.0, value2 = 300.0
/
&wt type = 'END'
/
But I am having following error in heat.out:-
Checking for mismatched coordinates.
Error : Atom 1 does not have match in V1 !
Also for *VDW stage*, I stripped off 1st charged ligand (BG0) from combined
PDB and used uncharged (BG1) ligand for vdw setup but I am getting:-
Molecule 1 is completely softcore and skipped for C.O.M..
Molecule 2 is completely softcore and skipped for C.O.M..
Molecule 3 is completely softcore and skipped for C.O.M..
Molecule 4 is completely softcore and skipped for C.O.M..
Molecule 5 is completely softcore and skipped for C.O.M..
.
.
.
.
.
Molecule 2856 is completely softcore and skipped for C.O.M..
Molecule 2857 is completely softcore and skipped for C.O.M..
Number of triangulated 3-point waters found: 2854
Number of shake restraints removed in TI region 1 : 0
Number of shake restraints removed in TI region 2 : 0
Sum of charges for TI region 1 = 0.00000000
Forcing neutrality...
Sum of charges for TI region 2 = 0.00000000
Forcing neutrality...
Summary of dvdl values over 100000 steps:
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
0.0000
I used following input for this step:-
TI simulation
&cntrl
imin = 0, nstlim = 100000, irest = 1, ntx = 5, dt = 0.002,
ntt = 3, temp0 = 300.0, gamma_ln = 2.0, ig = -1,
ntc = 2, ntf = 1,
ntb = 2,
ntp = 1, pres0 = 1.0, taup = 2.0,
ioutfm = 1, iwrap = 1,
ntwe = 1000, ntwx = 10000, ntpr = 10000, ntwr = 20000,
icfe = 1, clambda = 0.0, scalpha = 0.5, scbeta = 12.0,
logdvdl = 1,
ifmbar = 1, mbar_states= 11,
mbar_lambda= 0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6, 0.7, 0.8, 0.9, 1.0
bar_intervall = 10,
timask1 = ':BG1', timask2 = '',
ifsc=1, scmask1=':BG1', scmask2='',
/
&ewald
/
I need your suggestions, please.
Thank you
Sadaf
On Mon, Oct 14, 2019 at 9:03 PM Charles Lin <Charles.lin.silicontx.com>
wrote:
> For VDW you shouldn't have BG1 in your system at all (like delete it out
> of your pdb you're using to generate your inputs).
>
> icfe = 1
> timask1 = ':BG0', (fully charged)
> timask2 = '',
> ifsc = 1,
> scmask1 = ':BG0',
> scmask2 = '',
> crgmask = ':BG0',
>
> On 10/14/19, 3:03 PM, "Sadaf Rani" <sadafrani6.gmail.com> wrote:
>
>
> CAUTION: EXTERNAL EMAIL
>
>
>
> Dear Charles
> Thank you very much for your reply.
> As much I understand regarding my system in which I am using linear
> scaling
> scheme for decharge I have to do:-
> icfe = 1
> timask1 = ':BG0', (fully charged)
> timask2 = ':BG1', (no charge)
> ifsc = 0,
>
> and for VDW:-
>
> icfe = 1
> timask1 = ':BG0', (fully charged)
> timask2 = ':BG1', (no charge)
> ifsc = 1,
> scmask1 = ':BG0',
> scmask2 = ':BG1',
> crgmask = ':BG0 | BG1',
>
>
> thanks for your suggestions
>
> Sadaf
>
>
> On Mon, Oct 14, 2019 at 5:58 PM Charles Lin <Charles.lin.silicontx.com
> >
> wrote:
>
> > In absolute binding free energies, your endpoints are:
> > Ligand (fully charge, fully interacting), ligand (no charge full
> > interacting), nothing (no charge not interacting)
> >
> > Decharge does (fully charge, fully interacting) -> (no charge, fully
> > interacting)
> > VDW does (no charge, fully interacting) -> (no charge, not
> interacting)
> >
> > Therefore you don't need a recharge step.
> >
> > Essentially timask1 and timask2 define your endpoints of your lambda
> > windows (0.0 and 1.0).
> >
> > On 10/14/19, 11:11 AM, "Sadaf Rani" <sadafrani6.gmail.com> wrote:
> >
> >
> > CAUTION: EXTERNAL EMAIL
> >
> >
> >
> > Dear Amber and Charles
> > In this case, do I need to run a recharge state also?
> > Could you please brief a bit more, As I am trying this for the
> first
> > time I
> > have confusion about setting up the system that when I am using
> vdw
> > interactions does it contains parameters of both states? and for
> > decharge I
> > need to strip the first state?
> > I need your suggestions, please.
> > Thank you
> > Sadaf
> >
> >
> > On Mon, Oct 14, 2019 at 3:20 PM Charles Lin <
> Charles.lin.silicontx.com
> > >
> > wrote:
> >
> > > You shouldn't use softcore if your coordinates are being scaled
> > together
> > > (turn off both your scmasks). Yea the chargemask literally
> just
> > sets the
> > > charge of the atoms you indicate to 0, so you could have done
> it
> > through
> > > the parameterization or through the crgmask flag, so that's
> working
> > as
> > > intended.
> > >
> > > On 10/14/19, 6:59 AM, "Sadaf Rani" <sadafrani6.gmail.com>
> wrote:
> > >
> > >
> > > CAUTION: EXTERNAL EMAIL
> > >
> > >
> > >
> > > Dear Charles
> > > I set my system in which BG0 library contains charges
> however
> > there is
> > > no
> > > charge for BG1 state and I combined the two with same
> > coordinates and
> > > parameters in the same file after that I run a short
> > minimization with
> > > inputs as below:-
> > >
> > > minimization
> > >
> > > &cntrl
> > >
> > > imin = 1, ntmin = 2,
> > >
> > > maxcyc = 100,
> > >
> > > ntpr = 20, ntwe = 20,
> > >
> > > ntb = 1,
> > >
> > > ntr = 1, restraint_wt = 5.00,
> > >
> > > restraintmask='!:WAT & !.H=',
> > >
> > >
> > >
> > > icfe = 1, ifsc = 1, clambda = 0.5, scalpha = 0.5,
> scbeta =
> > 12.0,
> > >
> > > logdvdl = 0,
> > >
> > > timask1 = ':BG0', timask2 = ':BG1',
> > >
> > > scmask1 = ':BG0', scmask2 = ':BG1'
> > >
> > > crgmask=':BG1'
> > >
> > > /
> > >
> > > &ewald
> > >
> > > /
> > >
> > >
> > >
> > > It gives me following in output calculation:-
> > >
> > > 5. REFERENCE ATOM COORDINATES
> > >
> > > default_name
> > >
> > > Mask !:WAT & !.H=; matches 32 atoms
> > > TI Mask 1 :BG0; matches 27 atoms
> > > TI Mask 2 :BG1; matches 27 atoms
> > > TI region 1: 8682 atoms
> > > TI region 2: 8682 atoms
> > > SC Mask 1 :BG0; matches 27 atoms
> > > SC Mask 2 :BG1; matches 27 atoms
> > > Removing charge of 0.0000 from atom 28
> > > Removing charge of 0.0000 from atom 29
> > > Removing charge of 0.0000 from atom 30
> > > Removing charge of 0.0000 from atom 31
> > > Removing charge of 0.0000 from atom 32
> > > Removing charge of 0.0000 from atom 33
> > > Removing charge of 0.0000 from atom 34
> > > Removing charge of 0.0000 from atom 35
> > > Removing charge of 0.0000 from atom 36
> > > Removing charge of 0.0000 from atom 37
> > > Removing charge of 0.0000 from atom 38
> > > Removing charge of 0.0000 from atom 39
> > > Removing charge of 0.0000 from atom 40
> > > Removing charge of 0.0000 from atom 41
> > > Removing charge of 0.0000 from atom 42
> > > Removing charge of 0.0000 from atom 43
> > > Removing charge of 0.0000 from atom 44
> > > Removing charge of 0.0000 from atom 45
> > > Removing charge of 0.0000 from atom 46
> > > Removing charge of 0.0000 from atom 47
> > > Removing charge of 0.0000 from atom 48
> > > Removing charge of 0.0000 from atom 49
> > > Removing charge of 0.0000 from atom 50
> > > Removing charge of 0.0000 from atom 51
> > > Removing charge of 0.0000 from atom 52
> > > Removing charge of 0.0000 from atom 53
> > > Removing charge of 0.0000 from atom 54
> > > Total charge of 0.00000000 removed from 27 atoms
> > >
> > >
> > > Am I doing right? crgmask=':BG1' indicates that charges
> are
> > already
> > > removed from the BG1 state then why I am getting this
> charge
> > removal
> > > data
> > > is regarding BG1?
> > > I have attached the output file for reference.
> > > I need your guideline, please.
> > > thank you in advance.
> > >
> > > Sadaf
> > >
> > >
> > > On Thu, Oct 10, 2019 at 7:51 PM Charles Lin <
> > Charles.lin.silicontx.com
> > > >
> > > wrote:
> > >
> > > > Yea you basically want an identical copy of the ligand
> (same
> > > parameters,
> > > > same coordinates). You can use the combine call in
> tleap to
> > create a
> > > > topology this way (similar to how you use the combine
> call in a
> > > relative
> > > > binding free energy calculation.
> > > >
> > > > On 10/10/19, 10:45 AM, "Sadaf Rani" <
> sadafrani6.gmail.com>
> > wrote:
> > > >
> > > >
> > > > CAUTION: EXTERNAL EMAIL
> > > >
> > > >
> > > >
> > > > Dear Charles
> > > > thank you for your reply
> > > > I am a bit confused here. For system set up do I
> need to
> > build a
> > > second
> > > > copy of ligand (BG7) mentioned above which has no
> charge
> > on it
> > > and
> > > > save the
> > > > coordinates of both states (BG6 & BG7) in the same
> prmtop
> > file?
> > > > Could you please elaborate a little more regarding
> the
> > setting
> > > up of
> > > > system?
> > > > Also for vdw state, should I set my system like this?
> > > >
> > > > icfe = 1, clambda = 0.0, scalpha = 0.5, scbeta =
> 12.0,
> > > > logdvdl = 1,
> > > >
> > > > ifmbar = 1, mbar_states= 11,
> > > >
> > > > mbar_lambda= 0.0, 0.1, 0.2, 0.3, 0.4, 0.5, 0.6,
> 0.7,
> > 0.8,
> > > 0.9, 1.0
> > > >
> > > > bar_intervall = 10,
> > > >
> > > > timask1 = ':BG6', timask2 = '',
> > > >
> > > > ifsc = 1, crgmask = ':BG7',
> > > > scmask1=':BG6' scmask2='BG7'
> > > > crgmask=':BG6'
> > > >
> > > > looking forward to hear from you soon.
> > > >
> > > > Thank you
> > > >
> > > > Sadaf
> > > >
> > > >
> > > > On Thu, Oct 10, 2019 at 2:13 PM Charles Lin <
> > > Charles.lin.silicontx.com
> > > > >
> > > > wrote:
> > > >
> > > > > For decharge step you generally want your
> endstates to
> > be:
> > > > > Lambda 0: Molecule with charge
> > > > > Lambda 1.0: Molecule without charge
> > > > >
> > > > > Therefore you'd want 2 copies of your ligand.
> > > > >
> > > > > So you'd want
> > > > > Timask1=':BG6', timask2=':BG7' (or whatever second
> copy
> > of your
> > > > ligand is)
> > > > > crgmask=':BG7'
> > > > >
> > > > > On 10/10/19, 8:16 AM, "Sadaf Rani" <
> sadafrani6.gmail.com
> > >
> > > wrote:
> > > > >
> > > > >
> > > > > CAUTION: EXTERNAL EMAIL
> > > > >
> > > > >
> > > > >
> > > > > Dear Amber and Charlie
> > > > > I run TI calculation for calculating absolute
> free
> > energy
> > > > calculation
> > > > > of
> > > > > ligand with the following input in decharge
> step:-
> > > > >
> > > > > icfe = 1, clambda = 0.0, scalpha = 0.5, scbeta
> =
> > 12.0,
> > > > > logdvdl = 1,
> > > > >
> > > > > ifmbar = 1, mbar_states= 11,
> > > > >
> > > > > mbar_lambda= 0.0, 0.1, 0.2, 0.3, 0.4, 0.5,
> 0.6,
> > 0.7,
> > > 0.8,
> > > > 0.9, 1.0
> > > > >
> > > > > bar_intervall = 10,
> > > > >
> > > > > timask1 = ':BG6', timask2 = '',
> > > > >
> > > > > ifsc = 0, crgmask = ':BG6',
> > > > >
> > > > > but it gives me following error:-
> > > > >
> > > > > TI Mask 1 :BG6; matches 27 atoms
> > > > > TI Mask 2 matches 0 atoms
> > > > > TI region 1: 8591 atoms
> > > > > TI region 2: 8564 atoms
> > > > > Removing charge of -0.6555 from atom
> 1
> > > > > Removing charge of 0.4043 from atom
> 2
> > > > > Removing charge of 0.1047 from atom
> 3
> > > > > Removing charge of 0.0443 from atom
> 4
> > > > > Removing charge of 0.2450 from atom
> 5
> > > > > Removing charge of -0.7348 from atom
> 6
> > > > > Removing charge of 0.4283 from atom
> 7
> > > > > Removing charge of -0.0045 from atom
> 8
> > > > > Removing charge of 0.2380 from atom
> 9
> > > > > Removing charge of -0.7107 from atom
> 10
> > > > > Removing charge of 0.4056 from atom
> 11
> > > > > Removing charge of 0.0704 from atom
> 12
> > > > > Removing charge of 0.5188 from atom
> 13
> > > > > Removing charge of -0.7055 from atom
> 14
> > > > > Removing charge of 0.4528 from atom
> 15
> > > > > Removing charge of -0.0204 from atom
> 16
> > > > > Removing charge of -0.5253 from atom
> 17
> > > > > Removing charge of 0.2104 from atom
> 18
> > > > > Removing charge of 0.0424 from atom
> 19
> > > > > Removing charge of 0.2913 from atom
> 20
> > > > > Removing charge of -0.0024 from atom
> 21
> > > > > Removing charge of -0.0024 from atom
> 22
> > > > > Removing charge of -0.5859 from atom
> 23
> > > > > Removing charge of 1.3045 from atom
> 24
> > > > > Removing charge of -0.9377 from atom
> 25
> > > > > Removing charge of -0.9377 from atom
> 26
> > > > > Removing charge of -0.9377 from atom
> 27
> > > > > Total charge of -2.00000000 removed from
> 27
> > atoms
> > > > >
> > > > > MBAR - lambda values considered:
> > > > > 11 total: 0.0000 0.1000 0.2000 0.3000
> 0.4000
> > 0.5000
> > > 0.6000
> > > > > 0.7000
> > > > > 0.8000 0.9000 1.0000
> > > > > Extra energies will be computed 10000
> times.
> > > > > Checking for mismatched coordinates.
> > > > > ERROR: timask1/2 must match the same
> number of
> > atoms
> > > for
> > > > > non-softcore
> > > > > run
> > > > >
> > > > > how should I set input to fix this error
> > > > > Looking forward to hearing from you.
> > > > > thank you
> > > > >
> > > > > Sadaf
> > > > >
> > > > > On Thu, Oct 3, 2019 at 5:13 PM Charles Lin <
> > > > Charles.lin.silicontx.com>
> > > > > wrote:
> > > > >
> > > > > > You essentially just need to run your
> production
> > scheme
> > > with
> > > > > different
> > > > > > lambdas by changing the clambda value.
> > > > > >
> > > > > > 0.0 = your ligand fully exists
> > > > > > 1.0 = your ligand has fully disappeared.
> > > > > >
> > > > > > Follow the folder setup like this:
> > > > > >
> > > http://ambermd.org/tutorials/advanced/tutorial9/index.html
> > > > > >
> > > > > > You may want to increase the number of lambda
> > windows
> > > you're
> > > > using
> > > > > because
> > > > > > your transformation is a lot bigger when
> you're
> > > augmenting both
> > > > > > electrostatics and vdws. You may want to
> > considering
> > > doing it
> > > > in
> > > > > two steps
> > > > > > where you first decharge your molecule then
> > disappear
> > > the vdws.
> > > > > (Similar
> > > > > > to the tutorial except scmask2 and timask2
> are
> > both '',
> > > and you
> > > > > don't run a
> > > > > > recharge window.
> > > > > >
> > > > > > -Charlie
> > > > > >
> > > > > > On 10/3/19, 11:06 AM, "Sadaf Rani" <
> > sadafrani6.gmail.com
> > > >
> > > > wrote:
> > > > > >
> > > > > >
> > > > > > CAUTION: EXTERNAL EMAIL
> > > > > >
> > > > > >
> > > > > >
> > > > > > Dear Amber
> > > > > > I am also looking for the same.
> > > > > > I have a ligand for my protein for which
> I
> > want to
> > > > calculate
> > > > > absolute
> > > > > > binding energy; in which I want the
> ligand to
> > > disappear
> > > > > completely at
> > > > > > the
> > > > > > start and then appear with all vander
> waals and
> > > > electrostatic
> > > > > > interactions.
> > > > > > As per my understanding(I may be wrong
> in
> > it), I
> > > should
> > > > set up
> > > > > my
> > > > > > ligand
> > > > > > in solution and complex in solution as
> per the
> > > following
> > > > input:-
> > > > > > Minimization:-
> > > > > > &cntrl
> > > > > > imin = 1, ntmin = 2,
> > > > > > maxcyc = 1000,
> > > > > > ntpr = 200, ntwe = 200,
> > > > > > ntb = 1,
> > > > > > ntr = 1, restraint_wt = 5.00,
> > > > > > restraintmask='!:WAT & !.H=',
> > > > > >
> > > > > > icfe = 1, ifsc = 1, clambda = 0.0,
> scalpha
> > = 0.5,
> > > > scbeta =
> > > > > 12.0,
> > > > > > logdvdl = 0,
> > > > > > timask1=':1', scmask1=':1',
> > > > > > timask2='', scmask2='',
> > > > > > /
> > > > > > &ewald
> > > > > > /
> > > > > >
> > > > > > Heating:-
> > > > > > &cntrl
> > > > > > imin = 0, nstlim = 10000, irest = 0,
> ntx =
> > 1, dt =
> > > > 0.002,
> > > > > > nmropt = 1,
> > > > > > ntt = 1, temp0 = 300.0, tempi = 5.0,
> tautp
> > = 1.0,
> > > > > > ntb = 1,
> > > > > > ntc = 2, ntf = 1,
> > > > > > ioutfm = 1, iwrap = 1,
> > > > > > ntwe = 1000, ntwx = 1000, ntpr =
> 1000, ntwr
> > =
> > > 5000,
> > > > > >
> > > > > > ntr = 1, restraint_wt = 5.00,
> > > > > > restraintmask='!:WAT & !.H=',
> > > > > >
> > > > > > icfe = 1, ifsc = 1, clambda = 0.5,
> scalpha
> > = 0.5,
> > > > scbeta =
> > > > > 12.0,
> > > > > > logdvdl = 0,
> > > > > > timask1=':1', scmask1=':1',
> > > > > > timask2='', scmask2='',
> > > > > > /
> > > > > > &ewald
> > > > > > /
> > > > > >
> > > > > > &wt
> > > > > > type='TEMP0',
> > > > > > istep1 = 0, istep2 = 8000,
> > > > > > value1 = 5.0, value2 = 300.0
> > > > > > /
> > > > > >
> > > > > > &wt type = 'END'
> > > > > > /
> > > > > >
> > > > > > Pressurizing:-
> > > > > > &cntrl
> > > > > > imin = 0, nstlim = 10000, irest = 1,
> ntx =
> > 5, dt =
> > > > 0.002,
> > > > > > ntt = 1, temp0 = 300.0, tautp = 1.0,
> > > > > > ntp = 1, pres0 = 1.0, taup = 2.0,
> > > > > > ntb = 2,
> > > > > > ntc = 2, ntf = 1,
> > > > > > ioutfm = 1, iwrap = 1,
> > > > > > ntwe = 1000, ntwx = 1000, ntpr =
> 1000, ntwr
> > =
> > > 5000,
> > > > > >
> > > > > > ntr = 1, restraint_wt = 5.00,
> > > > > > restraintmask='!:WAT & !.H=',
> > > > > >
> > > > > > icfe = 1, ifsc = 1, clambda = 0.5,
> scalpha
> > = 0.5,
> > > > scbeta =
> > > > > 12.0,
> > > > > > logdvdl = 0,
> > > > > > timask1=':1', scmask1=':1',
> > > > > > timask2='', scmask2='',
> > > > > > /
> > > > > > &ewald
> > > > > > /
> > > > > > What next? How to set input for absolute
> free
> > energy
> > > > > calculations in
> > > > > > order
> > > > > > to disappear ligand and slowly appear
> with
> > increase
> > > in
> > > > lambda?
> > > > > >
> > > > > > Looking for your kind suggestions,
> please.
> > > > > >
> > > > > > Thank you
> > > > > >
> > > > > >
> > > > > > On Wed, Oct 2, 2019 at 4:20 PM Charles
> Lin <
> > > > > Charles.lin.silicontx.com>
> > > > > > wrote:
> > > > > >
> > > > > > > Hi,
> > > > > > >
> > > > > > > I'd follow mostly the same protocol as
> a
> > relative
> > > > binding free
> > > > > energy
> > > > > > > (where ligand a transforms to ligand
> b), but
> > > instead of
> > > > having
> > > > > a
> > > > > > ligand b,
> > > > > > > your timask, scmask of those regions
> becomes
> > > nothing
> > > > > > > timask2='', scmask2='',
> > > > > > >
> > > > > > > I would also apply the virtual bond
> algorithm
> > > described
> > > > here
> > > > > to keep
> > > > > > your
> > > > > > > ligand in the pocket (described as a
> virtual
> > bond
> > > here)
> > > > > > >
> > https://pubs.acs.org/doi/pdf/10.1021/jp505777n
> > > > > > >
> > > > > > > These calculations are fairly
> expensive to
> > > calculate.
> > > > Relative
> > > > > > binding
> > > > > > > free energies converge a lot more
> quickly
> > because
> > > the
> > > > amount of
> > > > > > phase space
> > > > > > > to sample is already somewhat more
> limited
> > due to
> > > the
> > > > presence
> > > > > of a
> > > > > > ligand
> > > > > > > you already know its binding
> pose/pocket
> > > position. The
> > > > less
> > > > > data
> > > > > > you know
> > > > > > > about your system, the less likely
> you'll
> > place
> > > your
> > > > ligand
> > > > > > correctly, and
> > > > > > > simple changes such as having a side
> chain
> > > incorrect,
> > > > could
> > > > > vastly
> > > > > > give
> > > > > > > different absolute binding free energy
> > values.
> > > > > > >
> > > > > > > -Charlie
> > > > > > >
> > > > > > > On 10/1/19, 4:26 PM, "Debarati
> DasGupta" <
> > > > > > debarati_dasgupta.hotmail.com>
> > > > > > > wrote:
> > > > > > >
> > > > > > >
> > > > > > > CAUTION: EXTERNAL EMAIL
> > > > > > >
> > > > > > >
> > > > > > >
> > > > > > > Dear All,
> > > > > > >
> > > > > > > I have been trying to read more
> about
> > free
> > > energy
> > > > > calculations
> > > > > > using
> > > > > > > TI method implemented in AMBER18. I
> recently
> > did a
> > > > webinar by
> > > > > CCG
> > > > > > group
> > > > > > > wherein in MOE2019 they have
> incorporated
> > the TI
> > > > > implementation setup
> > > > > > > collaborating with AMBER.
> > > > > > >
> > > > > > > I did read this publication too
> from
> > Professor
> > > Carlos
> > > > > > Simmerling’s
> > > > > > > webpage “
> > > > > > >
> > > > > >
> > > > >
> > > >
> > >
> >
> https://chemrxiv.org/articles/Blinded_Prediction_of_Protein-Ligand_Binding_Affinity_Using_Amber_Thermodynamic_Integration_for_the_2018_D3R_Grand_Challenge_4/8312375/1
> > > > > > > ”
> > > > > > > This did throw a lot of light on
> how to
> > > exactly
> > > > setup TI
> > > > > > calculations
> > > > > > > in AMBER.
> > > > > > >
> > > > > > > I still have a very fundamental
> > question, it
> > > may be
> > > > very
> > > > > stupid,
> > > > > > but I
> > > > > > > am not sure how to setup TI to
> calculate the
> > > absolute
> > > > binding
> > > > > > affinity of a
> > > > > > > ligand towards a protein.
> > > > > > > Is there something I am missing
> totally?
> > > > > > > My protein of interest is
> ABL-kinase and
> > I
> > > have a
> > > > done some
> > > > > > co-solvent
> > > > > > > simulations to get some hotspots(
> areas of
> > possible
> > > > > ligandibility);
> > > > > > I need
> > > > > > > to calculate the binding affinity of
> these
> > small
> > > > cosolvents
> > > > > towards
> > > > > > ABL.
> > > > > > > TI methods give us a “deldelG”,
> which is
> > > relative
> > > > binding
> > > > > > affinity, if
> > > > > > > we have a receptor (say CathepsinS)
> and have
> > a set
> > > of 10+
> > > > > ligands
> > > > > > with a
> > > > > > > common core (scaffold).
> > > > > > > If I have one protein +1 ligand
> and I
> > need to
> > > > calculate the
> > > > > > binding
> > > > > > > affinity what is the procedure to be
> adopted?
> > > > > > > Is there a tutorial to do that?
> > > > > > >
> > > > > > > I am not looking to do MMGBSA/PBSA
> on
> > this
> > > system.
> > > > > > >
> > > > > > > Thanks
> > > > > > >
> > > > > > >
> > _______________________________________________
> > > > > > > AMBER mailing list
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Received on Thu Oct 17 2019 - 07:30:02 PDT
