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6 CnQuest " * 1 * =" =, E " # * * ) * 8, * ) =" + 8 " 5 CDED4--- " F" G ) * " # * " " * ) G * ) G " (# * ) Cambridge Crystallgraphic Data Centre Cambridge Crystallgraphic Data Centre #DOXSIS HEADER CSD ENTRY 90 DOXSIS P R= COMPND NICOTINE MONOHYDROGEN IODIDE CRYST P111 C 68H ATOM 3I 140N 1 I1 68 NICO I1 ATOM N1 NICO 410 N C C ATOM C NICO C C C5 ATOM C NICO C C C8 ATOM C NICO C N C10 ATOM C NICO H H H3 ATOM C NICO H H H6 ATOM C NICO H H H9 ATOM C NICO H H H1 ATOM C NICO H H H15 ATOM C NICO ATOM N 910 NICO CONECT 1 0 CONECT 3 7 CONECT MASTER END

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7 H N O. 9 O O " ) OH HO H N H H NH 8 3 O NH * ) D " = + * ) # * * O O N O O *(+ + NH HN O O O O 1 5 Knwledge f intermlecular interactins Knwledge-based applicatin prgrams Data mining tls fr ligand-receptr cmplexes and IsStar Scatterplts IsStar - knwledge base f infrmatin abut intermlecular interactins SuperStar - prgram fr predicting binding pints in an enzyme active site SuperStar predictins based slely n IsStar data

intermlecular interactins Knwledge-based applicatin prgrams Data mining tls fr ligand-receptr cmplexes

8 IsStar Density Surfaces Química Cuántica Se pueden cmbinar ls rbitales atómics para dar rbitales mleculares Orbitales mleculares del agua Orbitales del xígen "0 Orbitales del hidrógen F 7, H> "B & H* $9' $9' 0 I1 $ 1 D4 1 J4 1 K' L $L 9' $B.' 81 M" 6 0 8& 1 3,!M 8?;1 " 6 0 8&4?4; 1 8J?;1 " 8?;1 3 J" & 5 5 *

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9 Gaussian Spartan $9 D6 ' * $ J ' Cn variables: h 1 l1 h l l1 a1 l a Cn valres: h h l c c 1 l1 h l 1 a1 h l 1 a h l 1 a h 1 l a h 1 l a h 1 l a l l 1.09 a F 7 7 ( $ / 9 A6 $6 0< 1 " " ' A6 A6 E' A$6 0 3 " 7 3 " ' > A $6 0 3 =.,!EE' G 5,$ >,!M' $ ' 1 J$6 0< 3,!' 6 A $9 D6 ' PM3 EF PRECISE HO (water) MOPAC input as a Z-matrix O H H AM1 EF PRECISE HO (water) MOPAC input in Cartesian crdinates O H H

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10 *. +!. * ( " " Calculate new gemetry -+ Read input Calculate gemetry Assign basis set Calculate integrals Initial guess %( Self-cnsistent Field Calculate atmic frces -+ Ppulatin analysis ( % ( Calculate new gemetry -+ Read input Calculate gemetry Assign parameters Self-cnsistent Field iteratins Calculate atmic frces -+ Ppulatin analysis! " # $% $%& '$' ()!* + *,'! -#.* #.* /01,' ! 7(879!+, + ' $,! '+ '+ *:)3*!,,!'*'!'+ )* )(' % & $ #"!, (/ SMILES Simplified Mlecular Input Line Entry Specificatin Rules 1. Atms are represented by atmic symbls: B, C, N, O, F, P, S, Cl, Br, and I.. Duble bnds are `=', triple bnds are `#'. 3. Branching is indicated by parentheses. 4. Ring clsures are indicated by pairs f matching digits. Examples Depictin SSMILES Name Remark C methane hydrgens fill nrmal valence CCO ethanl a single bnd is assumed t jin adjacent atms CC(=O)O acetic acid parentheses are used t indicate branching C1CCCCC1 cyclhexane bnds can als be represented by pairs f matching digits

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11 BABEL A prgram designed t intercnvert a number f file frmats currently used in mlecular mdelling Input type cdes: alc -- Alchemy file macmd -- Macrmdel file prep -- AMBER PREP file micr -- Micr Wrld file bs -- Ball and Stick file mmin -- MM Input file bgf -- MSI BGF file mmut -- MM Output file car -- Bisym.CAR file mm3 -- MM3 file bg -- Bgie file mmads -- MMADS file caccrt -- Caca Cartesian file mdl -- MDL MOLfile file cadpac -- Cambridge CADPAC file mlen -- MOLIN file charmm -- CHARMm file mpcrt -- Mpac Cartesian file c3d1 -- Chem3D Cartesian 1 file mpint -- Mpac Internal file c3d -- Chem3D Cartesian file mput -- Mpac Output file cssr -- CSD CSSR file pcmd -- PC Mdel file fdat -- CSD FDAT file pdb -- PDB file gstat -- CSD GSTAT file psin -- PS-GVB Input file dck -- Dck Database file psut -- PS-GVB Output file dpdb -- Dck PDB file msf -- Quanta MSF file feat -- Feature file schakal -- Schakal file fract -- Free Frm Fractinal file shelx -- ShelX file gamut -- GAMESS Output file smiles -- SMILES file gzmat -- Gaussian Z-Matrix file spar -- Spartan file gauut -- Gaussian 9 Output file semi -- Spartan Semi-Empirical file g94 -- Gaussian 94 Output file spmm -- Spartan Ml. Mechanics file gr96a -- GROMOS96 (A) file ml -- Sybyl Ml file gr96n -- GROMOS96 (nm) file ml -- Sybyl Ml file hin -- Hyperchem HIN file wiz -- Cnjure file sdf -- MDL Isis SDF file unixyz -- UniChem XYZ file m3d -- M3D file xyz -- XYZ file macml -- Mac Mlecule file xed -- XED file BABEL A prgram designed t intercnvert a number f file frmats currently used in mlecular mdelling Output type cdes: > ", > 8; diag -- DIAGNOTICS file i -- IDATM file t -- Alchemy file macml -- Mac Mlecule file bs -- Ball and Stick file k -- Macrmdel file bmin -- Batchmin Cmmand file micr -- Micr Wrld file caccrt -- Caca Cartesian file mi -- MM Input file cacint -- Caca Internal file m -- MM Ouput file cache -- CAChe MlStruct file mm3 -- MM3 file c3d1 -- Chem3D Cartesian 1 file mmads -- MMADS file c3d -- Chem3D Cartesian file mdl -- MDL Mlfile file d -- ChemDraw Cnn. Table file ac -- Mpac Cartesian file cn -- Cnjure file ai -- Mpac Internal file cntmp -- Cnjure Template file pc -- PC Mdel file cssr -- CSD CSSR file p -- PDB file feat -- Feature file reprt -- Reprt file fhz -- Fenske-Hall ZMatrix file spar -- Spartan file gamin -- Gamess Input file ml -- Sybyl Ml file gcart -- Gaussian Cartesian file ml -- Sybyl Ml file g -- Gaussian Z-matrix file maccs -- MDL Maccs file file gtmp -- Gaussian Z-matrix tmplt file xed -- XED file hin -- Hyperchem HIN file unixyz -- UniChem XYZ file icn -- Icn 8 file x -- XYZ file ftp://ccl.sc.edu/pub/chemistry/sftware/unix/babel/

CAR file mm3 -- MM3 file bg -- Bgie file mmads -- MMADS file caccrt -- Caca Cartesian file mdl -- MDL MOLfile file cadpac -- Cambridge CADPAC file mlen -- MOLIN file charmm -- CHARMm file mpcrt --

12 ) * α 7 α/β Binding Site Superpsitin Prtein-ligand database system Based n riginal sftware develped by Manfred Hendlich and clleagues at Merck and Marburg University Enables searching f PDB and f in-huse prprietary databases Relibase:

develped by Manfred Hendlich and clleagues at Merck and Marburg University Enables

13 Sme Relibase+ Optins Text searching Sequence searching D substructure and similarity searching 3D substructure searching Lgical cmbinatin f hit lists Searching fr intermlecular interactins Aut-superpsitin f similar binding sites Scripting facility based n Pythn Analysis f 3D searches Ligand Explrer variables VIP*! "# $% & "'"!!!

intermlecular interactins Aut-superpsitin f similar binding sites Scripting facility

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