[gmx-users] Linear Interaction Energy Method (LIE)

[Rajitha Tatikonda]

Hi,

I am trying to calculate ligand binding affinity of Dimeric Protein(198
residues) complexed with a peptide(3 residues) using Linear Interaction
Energy method.The water box dimensions  of ligand  with protein and Ligand
in water are considered to be same.
I am  encountering problem in estimating long range electrostatic
interactions for ligand interacting with solvent. I have used PME for
coulomb-type (trajectory length  is 1ns)  The option I used in g_energy to
extract  long range electrostatic interactions is Coul-Recip and results
appear to be strange since,the electrostatic energy(EE for ligand in
solvent are more negative than electrostatic for ligand in protein, which
implies positive values for delta EE(quite weird!)
I just wanted to know what are the proper mdp options in order to get
meaningful results and also what is the option in g_energy to get LR
interactions, whether usage of Coul-Recip is correct or not? I also want to
know the cutoffs to be mentioned in order  to calculate SR and LR.
Whether I should be using Reaction Field or cut-off for treatment of LR
interactions
The mdp file which I have been using is attached below
title        = Protein-Peptide Complex
; Run parameters
integrator    = md        ; leap-frog integrator
nsteps        = 500000    ; 2 * 500000 = 1000 ps, 1 ns
dt        = 0.002        ; 2 fs
; Output control
nstxout        = 1000        ; save coordinates every 2 ps
nstvout        = 1000        ; save velocities every 2 ps
nstxtcout    = 1000        ; xtc compressed trajectory output every 2 ps
nstenergy    = 1000        ; save energies every 2 ps
nstlog        = 1000        ; update log file every 2 ps
; Bond parameters
continuation    = yes        ; Restarting after NPT
constraint_algorithm = lincs    ; holonomic constraints
constraints    = all-bonds    ; all bonds (even heavy atom-H bonds)
constrained
lincs_iter    = 1        ; accuracy of LINCS
lincs_order    = 4        ; also related to accuracy
; Neighborsearching
ns_type        = grid        ; search neighboring grid cells
nstlist        = 5        ; 10 fs
rlist        = 0.5        ; short-range neighborlist cutoff (in nm)
rcoulomb    = 0.5        ; short-range electrostatic cutoff (in nm)
rvdw        = 1.0        ; short-range van der Waals cutoff (in nm)
; Electrostatics
coulombtype    = PME        ; Particle Mesh Ewald for long-range
electrostatics
pme_order    = 4        ; cubic interpolation
fourierspacing    = 0.16        ; grid spacing for FFT
; Temperature coupling is on
tcoupl        = V-rescale    ; modified Berendsen thermostat
tc-grps        = Protein Non-Protein     ; two coupling groups - more
accurate
tau_t        = 0.1    0.1    ; time constant, in ps
ref_t        = 300     300    ; reference temperature, one for each group,
in K
; Pressure coupling is on
pcoupl        = Parrinello-Rahman    ; Pressure coupling on in NPT
pcoupltype    = isotropic    ; uniform scaling of box vectors
tau_p        = 2.0        ; time constant, in ps
ref_p        = 1.0        ; reference pressure, in bar
compressibility = 4.5e-5    ; isothermal compressibility of water, bar^-1
pbc        = xyz        ; 3-D PBC
DispCorr    = EnerPres    ; account for cut-off vdW scheme
gen_vel        = no        ; Velocity generation is off

Many thanks in advance for your attention. I'd appreciate any help in this
regard.

Regards,
Hindu Tera