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
> > > > > > >
> > > > > > >
> > _______________________________________________
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Received on Thu Oct 17 2019 - 04:30:02 PDT
