FRODOCK tips

Written on 11 November 2016.

How to add constraints in the search?

The docking search can be constrained in two different ways.

Known receptor binding site:

Frodock allows to limit the translational exploration of the ligand location to a small region around a given position. This will be useful when the approximate possition of the ligand can be predicted. The option “−−around X,Y,Z” determine the 3D position central point of the desired translational exploration, and option -th specify the extension in amstrons.

Example:

../bin/frodock 3hfl_fv_ASA.pdb 1lza_ly2_ASA.pdb -w 3hfl_fv_W.ccp4 -e 3hfl_fv_E.ccp4 --th 10 -d 3hfl_fv_DS.ccp4,1lza_ly2_DS.ccp4 -o dock_C.dat --around 20.0,6.0,54.0
../bin/frodockcluster dock_C.dat 1lza_ly2.pdb --nc 100 -d 5.0 -o clust_dock_C.dat
../bin/frodockview clust_dock_C.dat -r 11 -p 1lza_ly2.pdb

This restriction allows to accelerate the docking search and avoid false predictions where the ligand is far from the receptor binding site.

Known aminoacids involved in the interaction:

A second way to discriminate solutions can be applied after the full docking search has been performed. The frodockonstraits application allows to select solutions that fulfill known conditions regarding proximity between ligand and receptor aminoacids in the interface. This constraints are stored input ASCII file like this:

RECEPT______LIGAND_____DIST 
-----------------------------------------
101          67        5.0

Using this file (constrainst.txt) the command will be:

../bin/frodockonstraints clust_dock2.dat 3hfl_fv.pdb 1lza_ly2.pdb constraints.txt -o clust_dock2_C.dat

This will create a file (clust_dock2_C.dat) with solutions that show at least a pair of atoms (no hydrogens) from receptor aminoacid 101 and ligand aminoacid 67 with a distant shorter than 5.0 Å. IMPORTANT: aminoacid number correspond to the order position of the aminoacid inside the PDB file.

The constraint file can contain many conditions, each one in a new line. To keep a solution, all conditions must be fulfilled. For example, this file:

RECEPT______LIGAND_____DIST
-----------------------------------------
101          67        5.0
102         -1        10.0
-1           68       10.0

contains three conditions. The first one implies that at least one atom pair from receptor aminoacid 101 and ligand aminoacid 67 must be closer than 5.0 Å. The second condition states that at least one atom from receptor aminoacid 101 must be to less than 10 Å of any atom from the ligand. The third states that at least one atom from ligand aminoacid 68 must be to less than 10 Å of any atom from the receptor. The three conditions must be fulfilled to keep a solution.

../bin/frodockonstraints clust_dock2.dat 3hfl_fv.pdb 1lza_ly2.pdb constraints.txt -o clust_dock2_C.dat

How to set up MPI libraries?

The frodock_mpi binary files requires dynamic links to a set of MPI (version 1.4) and system libraries. If the corresponding frodock_mpi does not work correctly with your MPI installation, check whether the libraries are accessible by:

> ldd ../bin_MPI_VERSION/frodock_m

linux-gate.so.1 =>  (0xffffe000)
libmpi_cxx.so.0 => /usr/lib/openmpi/1.4-gcc/lib/libmpi_cxx.so.0 (0xf7f65000)
libmpi.so.0 => /usr/lib/openmpi/1.4-gcc/lib/libmpi.so.0 (0x00c29000)
libopen-rte.so.0 => /usr/lib/openmpi/1.4-gcc/lib/libopen-rte.so.0 (0x00b7d000)
libopen-pal.so.0 => /usr/lib/openmpi/1.4-gcc/lib/libopen-pal.so.0 (0x00b0c000)
libdl.so.2 => /lib/libdl.so.2 (0x00a04000)
libnsl.so.1 => /lib/libnsl.so.1 (0x00c0e000)
etc...

If any of the libraries listed is marked up as "Not Found" it will be necessary to install it or include its path in LD_LIBRARY_PATH (NOTE: It is possible that existing libraries present a different name, in that case a symbolic link could solve this problem).