rxdcpu1 / apbscore Goto Github PK

APBScore v0.1 (by Bao Jingxiao 2020.8)

Introduction--------------------------------------------------------------------
APBScore is a scoring function that mainly aimed at estimating the binding free
energy between protein receptor and small organic ligand. It is a physical-based
scoring function and has three terms including atom pairwised van der Waals
energy, electrostatic energy and hydrogen bond energy between the receptor and
ligand. This scoring function is developed based on Amber force fields and
requires basic knowledge of Amber program (e.g. prepare ligand with antechamber,
build complex top and crd files with leap and run energy minimizations with 
sander or pmemd) to use.
--------------------------------------------------------------------------------

Make and Install----------------------------------------------------------------
0.Amber program is required before you can make and use APBScore. The NetCDF lib
  built by amber are required for making, antechamber and tleap are required to
  build the complex top and crd files, pmemd or sander is required to perform
  energy minimizations. Amber18+AmberTools19 were used during developing, so
  modifications may be required for other amber versions.

1.Open a shell terminal and cd to the "src" folder, edit the "Make.sh" file by
  changing the XXX of the 3rd line to the file path where your amber is
  installed (e.g. /home/paul/amber18). If your amber were not built with the GNU
  compiler, you will also need to change the fortran compiler to the compiler
  with which you built your amber, and the compiler options may also need to be
  changed.

2.Run "bash Make.sh" to make and install the APBScore program. The binary file
  named APBScore will be placed in the "bin" folder under the same directory as
  "src". Add the bin folder to your $PATH, or you can use the full path when
  run APBScore.
--------------------------------------------------------------------------------

Brief Example-------------------------------------------------------------------
0.There is a brief example in the "example" folder, we recommend you to backup
  this folder before testing. There are mainly three steps: 1) prepare receptor
  and ligand to get complex top and crd files, 2) run energy minimization in
  vacuum with internal dielectric constant set to 3.0, 3) calculate APBScore on
  the minimized structure. The first two steps require users to have basic
  knowledge about Amber program, you can visit "http://ambermd.org/tutorials/"
  for amber official tutorials.

1.The complex structure should first be split into a receptor file in PDB format
  (e.g. 1eby_protein_noWat.pdb) and a ligand file in Tripos Mol2 format (e.g.
  1eby_ligand.mol2). Waters should be removed from the receptor, and residue
  name and atom name should be adjusted to Amber format. Since the protonation
  states are controlled by residue name in Amber, hydrogen atoms are not
  necessary required in the receptor PDB file. All atoms including hydrogens are
  required for the ligand Mol2 file, and correct tripos atom type and bond order
  should be set.

2.The ligand is prepared with "LIG_Prepare.sh" by calculating the AM1-BCC atom
  charges and assigning gaff2 atom types with antechamber to get the
  "1eby_ligand_noOpt_BCC_gaff2.mol2" file, and assigning suitable force field
  parameters for missing parameters with parmchk2 to get the
  "1eby_ligand_gaff2.frcmod" file. Since we think the original ligand structure
  is reasonable, we do not perform structure optimizations during QM calculation
  (by adding "maxcyc=0" with "-ek" flag) to speed up the charge calculation.
  "scfconv=1.d-8" and "ndiis_attempts=700" are also added to make the scf more
  easy to convergence.

3.tleap is used to get the "COM.top" and "COM.crd" files with commands in the
  "tleap.in" file. The "leaprc.protein.ff14SB" force field is used for protein
  , "leaprc.gaff2" force field is used for ligand, "leaprc.water.tip3p" with
  "frcmod.ions1lm_126_tip3p" and "frcmod.ions234lm_126_tip3p" are used for ions.
  The FFPTM force field can be used for common post-translational modified
  residues. If there are disulfide bonds in receptor, they should be bond with
  the "bond" command in tleap.

4.The complex structure should then be minimized before scoring. During the
  developing of APBScore, several minimize methods were tested, and minimize in
  vacuum with internal dielectric constant set to 3.0 shown best performance
  when both accuracy and efficiency were considered. Run "bash Run_Minimize.sh"
  in the "Step2_Min_VAC_Diel3.0" folder to perform the minimizations. It will
  first call the "ChangeTopCharge.sh" script to get a temporary top file named
  "COM_mod.top" where the atom charges are reduced to sqrt(1/3) of the original.
  This is equivalent to set a internal dielectric constant to 3.0, as the
  electrostatic energy between atoms will be one third of the original.
  
5.Then, two stages minimizations will be performed. In the first stage, 10.0
  kcal/mol/A^2 constraints are added on all heavy atoms of the complex and 500
  steps steepest descent minimizations (SD) followed by 500 steps conjugate
  gradient minimizations (CG) will be performed. In the next stage, there will
  be no constraint, and the system will be minimized by 500 steps SD and 500
  steps CG. In the script, the minimizations will be calculated on GPU with
  pmemd.cuda, and the result rst file named "Com_min2.rst" will be used in
  scoring. If your Amber version is older than 16 (where igb=6 is not supported
  by pmemd.cuda), your can run the calculations on CPU with pmemd or pmemd.MPI.
  If you do not have Amber, you can use sander or sander.MPI, which is free of
  charge. However, the speed will be much slower when the calculations are run
  on CPU(s).

6.During the developing of APBScore, the energy minimizations were performed in
  a more complex way. The complex was first minimized with 10.0 kcal/mol/A^2
  constraints on all heavy atoms for 400 steps SD and 100 steps CG by pmemd.MPI
  on CPUs, then minimized without constraints for 400 steps SD and 100 steps CG
  by pmemd.MPI on CPUs, and finally minimized without constraints for 4500 steps
  SD and 4500 steps CG by pmemd.cuda on GPU. We have tested the performance of
  the minimize processes used in this example, and found that the scoring and
  ranking power were similarly as those reported in our APBScore paper.

7.After structure minimization, the APBScore can be calculated. A configure file
  is required, see "APBScore.config" in the "Step3_Score" folder for example.
  You will need to change the "file path" based on the location of your files.
  Remember to add "/" at the end of your path. The complex topology file name is
  COM.top and the restart file name is Com_min2.rst. This restart file must be
  in NetCDF format. There are 199 residues in the complex and 1 to 198 residues
  belong to the receptor while residue 199 is the ligand. The "fitting
  coefficient data file path and name" should also be adjusted base on your file
  location. The data file "APBScore_Fit_VAC_Diel3.0_123_Rst_kvdw.dat" in the
  "dat" folder under the same directory as the "example" folder records the
  fitted parameters for APBScore.

8.After modified the "APBScore.config" file, you can now run
  "../../bin/APBScore APBScore.config" to calculate the APBScore. The score is
  reported in the unit of kcal/mol. Since, only VDW interactions between
  receptor elements: H, C, N, O, S, Zn and ligand elements: H, C, N, O, P, S, F,
  Cl, Br, I are calculated in APBScore, a notice will be reported when there are
  other elements in receptor or ligand.

9.The score result of the minimized complex in this example is -11.5561. Since
  there will be small structure and energy differences between complexes
  minimized with different computers, or even on the same computer with
  different programs (i.e. sander, sander.MPI, pmemd, pmemd.MPI and pmemd.cuda),
  slight difference on the score calculated on the complex minimized by yourself
  is expected.
--------------------------------------------------------------------------------