What is DG-AMMOS How to install DG-AMMOS How to run DG-AMMOS Example References What is DG-AMMOS

DG-AMMOS (Distance Geometry and Automatic Molecular Mechanics Optimization for in silico Screening) [1] employs an automatic procedure for generation of 3D conformation of small molecules, based on distance geometry. s such, the soft!are offers "aluable solutions to assist structure#based or ligand#based in silico screening pro$ects. D%# &&'S has been de"eloped in the laboratory of (ioinformatics#&)*, *+S,-& ./03 1 .ni"ersity 2aris Diderot (http344!!!.mti.uni"#paris#diderot.fr4en4inde5.html). )he pac6age D%# &&'S is !ritten in 7 and 2ython and is a"ailable for 8inu5 and &ac 'S 9 systems under the %+. %eneral 2ublic license. D%# &&'S ma6es use of the program &&2 [:#3], a"ailable under %+. license (http344!!!.cs.gsu.edu4;cscr!h4ammp4ammp.html). &ultiple conformer ensembles can be generated after D%# &&'S by using the free tool &ulticonf#D'7< (http344!!!.mti.uni"#paris#diderot.fr4en4do!nloads.html= http344doc6.compbio.ucsf.edu47ontributed>7ode4multiconfdoc6.htm) [?] Please, cite Da!i" #a$orce, %ania Penche!a, &runo O 'illoutreix, an" Maria A Mite!a . D%# &&'S3 +e! tool to generate 3D conformation of small molecules using Distance %eometry and utomated &olecular &echanics 'ptimization for in silico Screening. @ou may direct Auestions related to this pac6age to the corresponding author3 &aria &ite"a, 2hD

Senior Scientist (ioinformatics#&)*, *+S,-& ./03 # .ni"ersity 2aris Diderot B rue &arie# ndrCe 8agroua, 0B:DB 2aris 7ede5 13, Erance ,#mail3 maria.mite"aFuni"#paris#diderot.fr D%# &&'S performs fast, automated and reliable access for generation of 3D conformation of small molecules and can be applied to libraries !ith a large number of compounds. )he entire procedure of D%# &&'S, from the input of small molecules (in mol: format) to the final built molecules (in mol: format) is sho!n in the follo!ing scheme3

PRE-AMMP

AMMP

4
mol2-to-ammp
For each compound performs conversion in ammp format

build_mol2_dgeom. ammp

3
mol2_to_templ
For each compound creates templates

6
ammp-to-mol2

Build mole cules base d on dista nce For each geo compound metr performs y conversio n from ammp to mol2 format

2
DG-AMMOS

INPUT OUTPUT

7
input.param energy file compound collection file (.mol2)

warnings file built molecules (.mol2)

(i$ure ). Schematic flo! of the D%# &&'S algorithm (ac6 to the top

How to install DG-AMMOS

Step ) *ncompress the pac+a$e in a #inux shell as follows > tar -zxvf DG-AMMOS.tar.gz )he directory ~DG-AMMOS contains the subdirectories3 Gbin4G3 e5ecutable binary files Gdoc4G3 user manual Gexample4G3 an e5ample for running D%# &&'S Ginstall4G Gprogs4G3 o Gammp4G3 the program &&2 o Gpreammp4G3 the program 2-, &&2 o GP t!on"scripts4G3 the 2ython scripts of D%# &&'S o Gvls"min4G3 the 7 programs source and input files for the D%# &&'S building protocol Step , -ompile the source co"es *n the ~DG-AMMOS#install subdirectory run the compiling script GMa$efileG by typing3 > ma$e )he script !ill compile the source codes automatically and !ill generate e5ecutable files for the programs &&2, 2-, &&2, and D%# &&'S. )his script !ill automatically install all e5ecutable files into the directory ~DG-AMMOS#bin4. (%arning3 you need 2ython :.B.1 to :.H.:) Step . .ser should edit the I.cshrcJ or I.bashrcJ file on a 8inu5 operating system, or the I.profileJ file on &ac 'S9 system, to add the path of ~DG-AMMOS#bin in PA&' en"ironment "ariable. Eor e5ample, in c#shell3 K set pat!()*pat! ~#DG-AMMOS#bin) (ac6 to the top

How to run DG-AMMOS

*n the !or6ing directory !here D%# &&'S computations !ill be ran, the follo!ing files should be present3 t!e compo+nd collection in mol, format and the inp+t parameter file (see for e5ample the inp+t.param file in the ~DG-AMMOS#example directory). )he user should edit this file to gi"e the correct path and chosen collection3 )he input parameter file3 3

path>of>DG-AMMOS L pat! of t!e pac$age DG-AMMOSban6 L name of t!e compo+nd collection in mol, format /ote3 )he total number of symbols of the path>of>DG-AMMOS should not e5ceed MD. )o run D%# &&'S for generation of 3D conformation of small molecules3 K dg-ammos.py inp+t"parameter"file D%# &&'S 2rocedure3 )he entire automatic procedure for generation of 3D conformation of small molecules !ith D%# &&'S, from the input file (the compound collection) to the output (the final created 3D conformation of compounds) is sho!n in figure 1. )he automatic procedure for a large number of small molecules is accomplished "ia a 2ython script. )he procedure mol,"to"templ"sp. )available in ~DG-AMMOS#progs#vls"min/ creates template files for the small molecules, based on the initial mol: file. Some !arning could appear if un6no!n atom types or bonds are present. )he preparation of small molecules in the specific ammp format is carried out !ith the program 2-, &&2 !hich is a part of the &&2 pac6age. )he input file reAuired by &&2 for the procedure of 3D conformation generation of small molecules is b+ild"mol,"dgeom.ammp (a"ailable in ~DG-AMMOS#progs#vls"min), !hich can be modified by the user. D%# &&'S ensures3 1) 6eeping the coordinates of the created 3D structures in mol: format. :) 6eeping the energy of the created structures. 3) 6eeping any !arning that may appear during the D%# &&'S run and I!rongJ generated molecules, if any, in terms of high energy. (ac6 to the top

Example
n e5ample of generation of 3D conformation of small molecules !ith D%# &&'S sho!ing the procedure is a"ailable in the directory ~DG-AMMOS#example. )he initial molecules in mol: format (inp+t"dataset.mol,) and the input parameter file (inp+t.param) (see e5planations abo"e) are pro"ided. .sers should edit the inp+t.param file and then run D%# &&'S by3 0 dg-ammos.py input.param )he results can be found in the directory ~DG-AMMOS#example3 N inp+t"dataset"0+ilt.mol, contains the coordinates of built molecules (see e5planations abo"e) N inp+t"dataset"0adMolec+les.mol, contains the coordinates of I!rongJ molecules !ith high energy if any (see e5planations abo"e) N inp+t"dataset"energ .txt contains the energy of molecules (see e5planations abo"e) ?

inp+t"dataset"total"1arnings.txt contains any !arning that can appear during the D%# &&'S run (see e5planations abo"e)

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References
1. Da!i" #a$orce, %ania Penche!a, &runo O 'illoutreix, an" Maria A Mite!a1 D%# &&'S3 +e! tool to generate 3D conformation of small molecules using Distance %eometry and utomated &olecular &echanics 'ptimization for in silico Screening. :. Oarrison -., 7. -eed, *. Peber. nalysis of 7omparati"e &odeling 2redictions for 7 S2: )argets 1, 3, /, and 10. Proteins2 Str+ct+re3 4+nction3 and Genetics, 1//0, Suppl. 1, HM#03 3. Peber *., -. Oarrison. &olecular &echanics 7alculations on 2rotein18igand 7omple5es. Perspectives in Dr+g Discover and Design, 1//M, /41D411, 11B#1:0 ?. Sauton +., D. 8agorce, (.'. Qilloutrei5, &. . &ite"a. &S#D'7<3 ccurate multiple conformation generator and rigid doc6ing protocol for multi#step "irtual ligand screening. 0M5 0ioinformatics, :DDM, /31M? (ac6 to the top