MODELLER A Program for Protein Structure Modeling Release 9v7, r6923 Andrej Saliˇ with help from Ben Webb, M.S. Madhusudhan, Min-Yi Shen, Marc A. Martı-Renom, Narayanan Eswar, Frank Alber, Maya Topf, Baldomero Oliva, Andr´as Fiser, Roberto S´anchez, Bozidar Yerkovich, Azat Badretdinov, Francisco Melo, John P. Overington, and Eric Feyfant email: modeller-care AT salilab.org URL http://salilab.org/modeller/ 2009/06/12 ii Contents Copyright notice xix Acknowledgments xxi 1 Introduction 1 1.1 What is Modeller?............................................. 1 1.2 Modeller bibliography.......................................... 2 1.3 Obtaining and installing the program . ........... 3 1.4 Bugreports........................................ .......... 4 1.5 Method for comparative protein structure modeling by Modeller ................... 5 1.6 Using Modeller forcomparativemodeling................................ 8 1.6.1 Preparing input files . ..... 8 1.6.2 Running Modeller ......................................... 9 2 Automated comparative modeling with automodel 11 2.1 Simpleusage ........................................ ......... 11 2.2 More advanced usage . ......... 12 2.2.1 Including water molecules, HETATM residues, and hydrogen atoms . ...... 12 2.2.2 Changing the default optimization and refinement protocol . ...... 14 2.2.3 Getting a very fast and approximate model . ......... 14 2.2.4 Building a model from multiple templates . ........ 15 2.2.5 Building an all hydrogen model . ........ 16 2.2.6 Refining only part of the model . ..... 16 2.2.7 Including disulfide bridges . 18 2.2.8 Providing your own restraints file . ............ 19 2.2.9 Using your own initial model . ......... 19 2.2.10 Adding additional restraints to the defaults . ........... 20 2.2.11 Building multi-chain models with symmetry . ........... 21 2.2.12 Accessing output data after modeling is complete . ....... 22 2.2.13 Fully automated alignment and modeling . ......... 23 2.3 Loopoptimization .................................. ............ 24 2.3.1 Automatic loop refinement after model building . ....... 24 2.3.2 Defining loop regions for refinement . ..... 25 2.3.3 Refining an existing PDB file . ...... 26 iii iv CONTENTS 3 Frequently asked questions and history 27 3.1 Frequently asked questions (FAQ) and examples . ......... 27 3.2 Modeller updates ............................................. 34 3.2.1 Changes since release 9v6 . ....... 34 3.2.2 Changes since release 9v5 . ....... 35 4 Comparative modeling class reference 37 4.1 automodel reference . 37 4.1.1 automodel() — prepare to build one or more comparative models . ......... 37 4.1.2 automodel.library schedule — select optimization schedule . 38 4.1.3 automodel.md level — control the model refinement level . 38 4.1.4 automodel.outputs — all output data for generated models . ...... 38 4.1.5 automodel.rand method — control initial model randomization . 38 4.1.6 automodel.generate method — control initial model generation . 38 4.1.7 automodel.max var iterations — select length of optimizations . 38 4.1.8 automodel.repeat optimization — number of times to repeat optimization . 38 4.1.9 automodel.max molpdf — objective function cutoff . 39 4.1.10 automodel.initial malign3d — initial template alignment . 39 4.1.11 automodel.starting model — first model to build . 39 4.1.12 automodel.ending model — last model to build . 39 4.1.13 automodel.final malign3d — final template-model alignment . 39 4.1.14 automodel.write intermediates — write intermediate files during optimization . 39 4.1.15 automodel.trace output — control optimization output . 39 4.1.16 automodel.get optimize actions() — get actions to carry out during the initial optimization . 39 4.1.17 automodel.get refine actions() — get actions to carry out during the refinement . 40 4.1.18 automodel.select atoms() — select region for optimization . 40 4.1.19 automodel.auto align() — generate an automatic initial alignment . 40 4.1.20 automodel.very fast() — request rapid optimization . 40 4.1.21 automodel.make() — build all models . ......... 40 4.1.22 automodel.cluster() — cluster all built models . ......... 40 4.1.23 automodel.special restraints() — add additional restraints . 41 4.1.24 automodel.nonstd restraints() — add restraints on ligands . 41 4.1.25 automodel.special patches() — add additional patches to the topology . 41 4.1.26 automodel.user after single model() — analyze or refine each model . 41 4.1.27 automodel.get model filename() — get the model PDB name . 41 4.1.28 automodel.use parallel job() — parallelize model building . 42 4.2 allhmodel reference . 42 4.2.1 allhmodel() — prepare to build all-hydrogen models . ........ 42 4.3 loopmodel reference . 42 4.3.1 loopmodel() — prepare to build models with loop refinement . ...... 42 4.3.2 loopmodel.loop.md level — control the loop model refinement level . 42 4.3.3 loopmodel.loop.max var iterations — select length of optimizations . 43 4.3.4 loopmodel.loop.library schedule — select optimization schedule . 43 4.3.5 loopmodel.loop.starting model — first loop model to build . 43 CONTENTS v 4.3.6 loopmodel.loop.ending model — last loop model to build . 43 4.3.7 loopmodel.loop.outputs — all output data for generated loop models . ......... 43 4.3.8 loopmodel.select loop atoms() — select region for loop optimization . 43 4.3.9 loopmodel.get loop model filename() — get the model PDB name . 43 4.3.10 loopmodel.user after single loop model() — analyze or refine each loop model . 43 4.3.11 loopmodel.read potential() — read in the loop modeling potential . 44 4.3.12 loopmodel.build ini loop() — create the initial conformation of the loop . 44 4.4 dope loopmodel reference.......................................... 44 4.4.1 dope loopmodel() — prepare to build models with DOPE loop refinement . 44 4.5 dopehr loopmodel reference......................................... 44 5 Modeller general reference 45 5.1 Miscellaneous rules and features of Modeller .............................. 45 5.1.1 Modeller system.......................................... 45 5.1.2 Controlling breakpoints and the amount of output . ........... 45 5.1.3 Filenaming...................................... ........ 45 5.1.4 Filetypes ...................................... ......... 46 5.2 Stereochemical parameters and molecular topology . ........... 46 5.2.1 Modeling residues with non-existing or incomplete entries in the topology and parameter libraries 47 5.3 Spatialrestraints .................................. ............. 47 5.3.1 Specification of restraints . .......... 48 5.3.2 Specification of pseudo atoms . ...... 50 5.3.3 Excluded pairs . ...... 52 5.3.4 Rigidbodies ..................................... ........ 52 5.3.5 Symmetryrestraints ............................... .......... 53 6 Modeller command reference 57 6.1 Key for command descriptions . ....... 57 6.2 The environ class: Modeller environment ............................... 57 6.2.1 environ() — create a new Modeller environment........................ 57 6.2.2 environ.io — default input parameters . ....... 58 6.2.3 environ.edat — default objective function parameters . ........ 58 6.2.4 environ.libs — Modeller libraries................................. 58 6.2.5 environ.schedule scale — energy function scaling factors . 58 6.2.6 environ.dendrogram() — clustering . ........ 58 6.2.7 environ.principal components() — clustering . 58 6.2.8 environ.system() — execute system command . ........ 59 6.2.9 environ.make pssmdb() — Create a database of PSSMs given a list of profiles . 59 6.3 The energy data class: objective function parameters . 61 6.3.1 energy data() — create a new set of objective function parameters . 61 6.3.2 energy data.contact shell — nonbond distance cutoff . 61 6.3.3 energy data.update dynamic — nonbond recalculation threshold . 61 6.3.4 energy data.sphere stdv — soft-sphere standard deviation . 62 6.3.5 energy data.dynamic sphere — calculate soft-sphere overlap restraints . 62 vi CONTENTS 6.3.6 energy data.dynamic lennard — calculate Lennard-Jones restraints . 62 6.3.7 energy data.dynamic coulomb — calculate Coulomb restraints . 62 6.3.8 energy data.dynamic modeller — calculate non-bonded spline restraints . 62 6.3.9 energy data.excl local — exclude certain local pairs of atoms . 62 6.3.10 energy data.radii factor—scaleatomicradii ........................... 62 6.3.11 energy data.lennard jones switch — Lennard-Jones switching parameters . 62 6.3.12 energy data.coulomb switch — Coulomb switching parameters . 63 6.3.13 energy data.relative dielectric — relative dielectric . 63 6.3.14 energy data.covalent cys — use disulfide bridges in residue distance . 63 6.3.15 energy data.nonbonded sel atoms — control interaction with picked atoms . 63 6.3.16 energy data.nlogn use — select non-bond list generation algorithm . 63 6.3.17 energy data.energy terms — user-defined global energy terms . 63 6.4 The io data class: coordinate file input parameters . 64 6.4.1 io data() — create a new input parameters object . 64 6.4.2 io data.hetatm — whether to read HETATM records . 64 6.4.3 io data.hydrogen — whether to read hydrogen atoms . 64 6.4.4 io data.water — whether to read water molecules . 64 6.4.5 io data.atom files directory — search path for coordinate files . 64 6.5 The Libraries class: stereochemical parameters and molecular topology . 65 6.5.1 Libraries.topology — topology library information . ................... 65 6.5.2 Libraries.parameters — parameter library information . .............. 65 6.5.3 Topology.append() — append residue topology library . ........... 65 6.5.4 Topology.clear()