Hello all<br><br>Earlier also I posted a query regarding FEP for protein ligand complex, but I dint not help much.<br>Again I would like to share detailed information regarding the protocol I am following for calculation the binding free energy between protein and ligand using FEP(free energy perturbation) method. Please correct me if I am wrong anywhere....as the values of <b>dVpot/dlambda dEkin/dlambda dG/dl constr </b>are continuously coming zero(0).<br>
<br>I followed the gromacs tutorial of protien-ligand complex (<a href="http://cinjweb.umdnj.edu/~kerrigje/pdf_files/trp_drug_tutor.pdf">http://cinjweb.umdnj.edu/~kerrigje/pdf_files/trp_drug_tutor.pdf</a>) for preparing the coordinate and topology file for the whole system.<br>
For Free energy Calculation I followed the tutorial (<a href="http://www.dillgroup.ucsf.edu/group/wiki/index.php/Free_Energy:_Tutorial">http://www.dillgroup.ucsf.edu/group/wiki/index.php/Free_Energy:_Tutorial</a>) for lambda value ranging from zero(0) to 1 and setup 11 independent job for each lambda value for 5 ns.<br>
But the<b> dVpot/dlambda dEkin/dlambda dG/dl constr</b> values in the *.log are continuously coming zero.<br>Any help will be highly appreciated.<br><br>For convenience I am also pasting my pro_constV.mdp (please let me know if any parameter is wrong of missing...which is leading to such problem)<br>
<br>; RUN CONTROL PARAMETERS =<br>integrator = md<br>; start time and timestep in ps =<br>tinit = 0<br>dt = 0.002<br>nsteps = 5000000<br>; number of steps for center of mass motion removal =<br>
nstcomm = 100<br>; OUTPUT CONTROL OPTIONS =<br>; Output frequency for coords (x), velocities (v) and forces (f) =<br>nstxout = 50000<br>nstvout = 50000<br>nstfout = 0<br>
; Output frequency for energies to log file and energy file =<br>nstlog = 500<br>nstenergy = 500<br>energygrps = protein non-protein<br>; Output frequency and precision for xtc file =<br>
nstxtcout = 5000<br>xtc-precision = 1000<br>; This selects the subset of atoms for the xtc file. You can =<br>; select multiple groups. By default all atoms will be written. =<br>;xtc_grps =<br>
; NEIGHBORSEARCHING PARAMETERS =<br>; nblist update frequency =<br>nstlist = 10<br>; ns algorithm (simple or grid) =<br>ns_type = grid<br>; Periodic boundary conditions: xyz or none =<br>
;pbc = xyz<br>; nblist cut-off =<br>rlist = 1.0<br>;domain-decomposition = no<br>; OPTIONS FOR ELECTROSTATICS AND VDW =<br>; Method for doing electrostatics =<br>coulombtype = pme<br>
;rcoulomb-switch = 0<br>rcoulomb = 1.0<br>; Dielectric constant (DC) for cut-off or DC of reaction field =<br>epsilon-r = 1<br>; Method for doing Van der Waals =<br>vdw-type = cut-off<br>
; cut-off lengths =<br>;rvdw-switch = 0.8<br>rvdw = 1.4<br>; Apply long range dispersion corrections for Energy and Pressure =<br>DispCorr = EnerPres<br>; Spacing for the PME/PPPM FFT grid =<br>
fourierspacing = 0.1<br>; FFT grid size, when a value is 0 fourierspacing will be used =<br>fourier_nx = 0<br>fourier_ny = 0<br>fourier_nz = 0<br>; EWALD/PME/PPPM parameters =<br>
pme_order = 6<br>ewald_rtol = 1e-06<br>epsilon_surface = 0<br>optimize_fft = yes<br>;restraints<br>;dihre=yes<br>;dihre-fc=1<br>;nstdihreout=1000<br>;disre=simple<br>;disre_fc=1<br>
; Berendsen temperature coupling is on<br>Tcoupl = berendsen<br>tau_t = 0.1 0.1<br>tc_grps = protein non-protein<br>ref_t = 300 300<br>;OPTIONS FOR PRESSURE COUPLING<br>Pcoupl = berendsen<br>tau_p = 0.5<br>
compressibility = 4.5e-05<br>ref_p = 1.0<br>; Free energy control stuff<br>free_energy = yes<br>init_lambda = 0.0<br>delta_lambda = 0<br>sc_alpha = 0.5<br>
sc-power = 1.0<br>sc-sigma = 0.3<br>; GENERATE VELOCITIES FOR STARTUP RUN =<br>gen_vel = yes<br>gen_temp = 300<br>gen_seed = 173529<br>; OPTIONS FOR BONDS =<br>
constraints = hbonds<br>; Type of constraint algorithm =<br>constraint-algorithm = Lincs<br>; Do not constrain the start configuration =<br>unconstrained-start = no<br>; Relative tolerance of shake =<br>
shake-tol = 0.0001<br>; Highest order in the expansion of the constraint coupling matrix =<br>lincs-order = 12<br>; Lincs will write a warning to the stderr if in one step a bond =<br>; rotates over more degrees than =<br>
lincs-warnangle = 30<br><br>
<br clear="all"><br>-- <br>Best Regards<br>SUNITA GUPTA<br>Member Research Team<br>LeadInvent Technology<br>TBIU, IIT Delhi, India<br>Email- <a href="mailto:sunita@leadinvent.com">sunita@leadinvent.com</a><br>Ph- +9111 26581524 (Ex-6)<br>
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