构象分析

᳝ᴎᇣߚᄤⱘᨁᓎⳂᷛ䗮䖛SYBYLᨁᓎϔϾ᳝ᴎᇣߚᄤҹᅠ៤㒧ᵘ䕧ܹˈ⏏ࡴǃᬍবॳᄤ៪ᅬ㛑ಶˈ᠟ᗻⱘᣛᅮˈ㒧ᵘӬ࣪ǃੑৡϢֱᄬDŽݙᆍᦤ⼎z㒧ᵘ䕧ܹzᅬ㛑ಶ⏏ࡴz᠟ᗻẔᶹǃবᤶz㒧ᵘӬ࣪zੑৡzֱᄬᡔᎻᦤ⼎೼SYBYL䞠䴶ˈ⬏㒧ᵘᓣⱘᯊ׭ˈϡৠѢ໻ᆊᐌ⫼ⱘChemofficeˈ≵᳝ᢪᣑ䖭Ͼ哴ᷛࡼ԰ˈা⫼⚍ߏህৃҹDŽϟϔϾॳᄤᛇ㽕⬏೼ા䞠ህ⚍ߏા䞠ˈ䆄ԣ˖ϡ㽕ᢪᣑDŽChapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorial 68SYBYL Basics SYBYL 8.18.1 Small Molecule Sketching TutorialBefore performing the following tutorial you should be familiar with thegraphics functions of SYBYL. If necessary, refer to the Quick Reference section in the Graphics Manual for a summary.•Preface on page 68•Set Up on page 69•Enter the Sketching Mode on page 69•Build Piperidine Ring in Chair Conformation on page 70•Add a Chain on page 72•Add a Group on page 73•Check Chirality on page 73•Clean Up on page 74•Save the Sketched Molecule on page 748.1.1 PrefaceIn this tutorial, you will build and minimize Atropine by building the mostcomplex ring system first and then adding the substituents. Typically, molecular fragments from the Standard Fragment Library are used to quickly constructring systems with good geometry. However, in order to better demonstrateSYBYL’s sketching capabilities, you will use the Sketch Molecule menuitems to construct and optimize the most complex ring system.After completing this tutorial, you will be able to:•Draw a ring •Minimize a ring system •Draw a chain •Add substituent groupsChapter 8. Build and Modify MoleculesSmall Molecule Sketching TutorialSYBYL 8.1SYBYL Basics 69•Check and assign chirality8.1.2 Set Up1.Clear the SYBYL screen of all molecules and background images.¾Edit > Clear All ¾Click theicon and press Everything (pressQ ). ¾Click the icon and set the Screen mode to Full (press Close ).8.1.3 Enter the Sketching Mode1.Display the sketch menus and select M1 as the work area in which to build themolecule.¾Edit > Sketch Molecule¾Select M1:<empty> (press OK ).Both a Sketch Molecule menu and an Atomic Symbol menu appear. You areautomatically placed in Draw mode so you can begin sketching immedi-ately.2.Display a grid to aid in building the molecule to scale. The spacing betweengrid points is 1.54 Å, the sp 3 carbon to sp 3 carbon bond length. The grid scales with the molecule in order to show the correct bond length.¾On the Sketch Molecule menu, press GridNote: If the grid gets in your way, toggle it off by pressing Grid again in theSketch Molecule menu.Chapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorial 70SYBYL Basics SYBYL 8.18.1.4 Build Piperidine Ring in Chair Conformation1.Build the ring as follows:¾Click in the middle of the screen.SYBYL displays a highlighted cross or small circle, representing an uncon-nected atom. The highlighting indicates that this atom is the current atom ofattachment and any subsequent point chosen is attached to this atom. Theatom is number 1 in the figure below.¾Click a point above this atom and approximately one grid spacing to the right (see atom 2 in the figure below).SYBYL draws a bond to the newly created second atom. ¾Continue sketching the 6-membered ring by clicking appropriate points on the screen.¾Close the ring by selecting atom 1 again.When you close the ring by picking atom 1, no atom is highlighted,indicating that continuous Draw mode is temporarily deactivated.Continuous mode is always suspended when an existing atom is chosen,whether it is the current atom of attachment or another atom. In the formercase, no bond is drawn; while in the latter case, a bond is drawn and thencontinuous draw mode is deactivated.2.Change the type of atom 1 to a nitrogen.¾On the Atomic Symbol menu, select N .Tip:Click to bring the Sketching and Atomic Symbol menus to the front.¾Click atom 1 on the sketched molecule.SYBYL displays a label indicating that the type has been successfullychanged and the atom is colored blue (on terminals supporting color).3.Introduce a third dimension to the molecule.¾Use the right mouse button and rotate the molecule about the X axisuntil it has an orientation similar to that shown in the figure below.Chapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorial4.Add the bridge across the ring.¾On the Sketch Molecule menu, select Draw to return to continuous Draw mode.¾Click atom 2 to make it the current attachment atom.¾Click a point below atom 2 and then another point diagonal to the new atom.¾Click atom 6 to close the ring.5.Clean up the ring system.¾On the Sketch Molecule menu, press TAILOR.¾Select CLEAN_UP (press OK).¾Select5_QUICK_MINIMIZE (press OK).¾On the Option dialog, press End.¾On the Sketch Molecule menu, press CLEAN_UP.There is an initial setup period while the minimizer parameters are being readfrom the database. Energy values are then printed in the text window after each iteration. The molecule display on the screen is not updated until the end of the minimization in order to reduce execution time. The minimization is completewhen the “Existing atom or new point:” prompt returns in the textport. SYBYL 8.1SYBYL Basics71Chapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorial 72SYBYL Basics SYBYL 8.18.1.5 Add a Chain1.Center the molecule on the screen.¾On the Sketch Molecule menu, select Center .¾Rotate the molecule until its orientation is similar to that shown in the figure below.2.Add a carbon chain to the ring.¾On the Sketch Molecule menu, select Move .¾Select atom 4 and click a point below the ring (roughly the same distance as N1 is above the ring).¾Select Draw .¾Select atom 4 as the current atom of attachment.¾Sketch the sidechain by picking (clicking) successive points at approximate locations on the screen for atoms 9 through 13.¾Click atom 13again to deactivate continuous Draw mode and end thechain.3.Draw a double bond for the carbonyl group.¾Click atom 10 as the new point of attachment and then click (pick) a point above the atom.¾Click atom 10 again.The double bond appears and continuous Draw mode is deactivated, sincean existing atom was chosen.Tip:If you can not see the double bond, rotate the molecule.Chapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorial4.Add a carbon to the nitrogen.¾Click atom 1, then a point to its left.¾Click that new atom again to deactivate continuous Draw mode.5.Sketch the ester and hydroxyl groups.¾Select O from the Atomic Symbol menu and then pick each of the three atoms: 9,13, and the end of the double-bond.The atoms are labeled with an O and colored red to reflect the change.8.1.6 Add a Group1.Access a list of predefined chemical groups and add a phenyl ring to themolecule.¾On the Sketch Molecule menu, press GROUP.¾Select PHENYL and click atom 11.2.Center the molecule.¾On the Sketch Molecule menu, press CENTER.¾Compare your sketch with atropine.8.1.7 Check ChiralityMake sure that atom 11 has a chirality of S.¾On the Sketch Molecule menu, press CHIRAL and click atom 11.¾Select S (press OK).If atom 11 is already an S chiral center, a message is displayed in thetextport informing you of this and nothing else happens. If, however, the R SYBYL 8.1SYBYL Basics73Chapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorialchiral center has been sketched, the center is inverted to assume the properstereochemistry.8.1.8 Clean Up1.Since the ring system has been already optimized, use the 4_SCAN option,which involves non ring bonds only, to clean up the model.Any clean up option from 1 to 6 includes all options preceding it in the list,therefore, all non-ring bonds have their bond lengths and angles adjusted, andthe torsion angles are scanned and adjusted to relieve bad contacts.¾On the Sketch Molecule menu, press TAILOR.¾Select CLEAN_UP (press OK).¾Select4_SCAN (press OK).¾Press End.¾On the Sketch Molecule menu, press CLEAN_UP.2.Add the necessary hydrogens to all unfilled valences.¾On the Sketch Molecule menu, press ADDH.All atom and bond types are automatically converted to SYBYL types,based on the connectivity prior to adding hydrogens.3.Exit from the sketching mode.¾On the Sketch Molecule menu, press EXIT.A final clean up is done automatically every time you exit the SketchMolecule menu.8.1.9 Save the Sketched Molecule the molecule.¾Edit > Name Molecule¾Type atropine (press OK).2.Save the full description of the molecule in a text file.¾File > Save As.74SYBYL Basics SYBYL 8.1Chapter 8. Build and Modify MoleculesSmall Molecule Sketching Tutorial ¾In the Save Molecule dialog, by default, atropine appears in the Filefield.¾By default, the Format is set to MOL2.¾Press Save.A file named atropine.mol2 is created in the current directory.In this tutorial, you built and minimized Atropine by building the most complex ring system first and then adding the substituents.When you work on your own research, you can use the same technique to save your molecules. To view them again, use the Open File dialog.This concludes the small molecule sketching tutorial. We suggest that yourepeat this tutorial with molecules from your own research.SYBYL 8.1SYBYL Basics75᳝ᴎᇣߚᄤⱘᨁᓎ㒗дᨁᓎᡫⳳ㦠㥃⠽Ӟ᳆ᒋ૥˄Itraconazole˅ˈ㒧ᵘᓣབϟ˖⊼ᛣ݊Ёⱘ᠟ᗻ⺇ⱘ㒱ᇍᵘൟDŽ᳔ৢᇚߚᄤֱᄬЎ˖Itraconazole_prac.mol2ᦤ⼎˖೼SYBYL䞠བԩẔᶹ᠟ᗻॳᄤⱘ㉏ൟSYBYL˖Edit>>>Find Chirality೼Type of isomerism䗝乍Ḛ䞠䗝ᢽRS⚍ߏOKᔍߎAtom Expressionᇍ䆱ḚˈऩߏAll៪Դᛳ݈䍷ⱘॳᄤ⚍ߏOK೼᭛ᴀにষህᦤ⼎Դˈાѯॳᄤ៪Դᛳ݈䍷ⱘॳᄤⱘ᠟ᗻ㉏ൟߚᄤ࡯എϢ㒧ᵘӬ࣪ⳂᷛᄺӮℷ⹂䗝ᢽ࡯എǃӬ࣪ᮍ⊩ᇍߚᄤ㒧ᵘ䖯㸠Ӭ࣪ˈᕫࠄড়⧚ⱘᵘ䈵DŽݙᆍᦤ⼎z䗝ᢽড়䗖ⱘߚᄤ࡯എ䖯㸠㛑䞣Ӭ࣪z䗝ᢽড়䗖ⱘӬ࣪ᮍ⊩䖯㸠㛑䞣Ӭ࣪z Փ⫼Match ঴ড়ৠϔߚᄤϡৠⱘᵘ䈵ˈᑊ䖯㸠↨䕗ᡔᎻᦤ⼎:ߚᄤ࡯എⱘ䗝ᢽϢӬ࣪ᮍ⊩ⱘ䗝ᢽߚᄤ࡯എⱘ䗝ᢽ೼乘⌟ߚᄤⱘ޴ԩᵘ䈵ˈ࡯എᰃϔ⾡䞡㽕ⱘᮍᓣDŽ࡯എ䳔㽕ձ᥂ⷨおᇍ䈵⡍⚍䖯㸠䗝ᢽˈ೼SYBYL Ёˈᦤկњ໮⾡Ӭ⾔ⱘ࡯എˈ໻ԧՓ⫼ᮍ⊩བϟ˖• “ ” means the force field was parameterized for this type of molecule,and is, thus, an excellent first choice for that particular class.• “ ” means the force field is also an acceptable choice and should be considered if the first choice lacks parameters or if a license for the first choice is unavailable, or to compare results between the different force fields.Force Field“Small” Molecule “Large” Molecule Protein-Liga nd Complex Metallo-prot eins Tripos2222Amber/Kollman11a MMFF94/MMFF94s 2211bӬ࣪ᮍ⊩ⱘ䗝ᢽ೼SYBYLЁˈᦤկњ໮⾡ⱘӬ࣪ᮍ⊩ҹࠄ䖒㛑䞣ߑ᭄ⱘሔ䚼ᵕᇣDŽ䖭ѯᮍ⊩䛑ᰃܜ䖯㸠⦄㸠᧰ᇏⱘDŽϟ䗄ⱘ㸼ḐЎ໻ᆊӬ࣪ᮍ⊩ⱘ䗝ᢽᦤկখ㗗˖Method Molecule Size RelativeSpeedOther NotesPowell Large or small Fastest Most efficientConjugate Gradient Small Slow Use when Powell fails to convergeSteepest Descent Small, with poorgeometryFast at highgradientsVery large stepsBFGS Small and with fewdegrees of freedomSlowest Very small stepsSYBYL introduction: minimization2Chapter 7.Minimize Energies•Minimizing Tutorial on page 181•Minimization Methods on page 194•Minimize Energy in SYBYL on page 196•Minimize a Structure via the Menubar on page 200•Minimize a Structure via Command Line on page 205•Minimize and Fit Multiple Structures on page 206Energy is a function of the atomic coordinates and the program attempts togenerate the coordinates which correspond to a minimum of energy. This isaccomplished by a minimization procedure. All the minimization methodscurrently used for this purpose are called descent series methods. They areiterative methods in which the atomic coordinates are modified from oneiteration to the next in order to decrease the energy.These methods are generally unable to find the global energy minimum of anybut very simple molecules, i.e., the set of atomic coordinates corresponding tothe lowest value of the energy. Most of the time, only a local minimum is found — the one closest to the starting set of coordinates. The only way to find theglobal minimum is to systematically explore different sets of starting coordi-nates. These can be generated by rigid geometry calculations (SEARCH,RANDOMSEARCH, or GRIDSEARCH) or postulated on the basis of other consider-ations and data (e.g., NMR studies or crystallographic results).Another problem is finding a minimum of the energy function for such a largenumber of variables: there are 3xN variables (Cartesian coordinates) tooptimize. Several optimization methods are available. Some use the atom-by-atom technique, where three Cartesian coordinates of one atom are optimizedsimultaneously. Others optimize the orientation of groups of atoms as a whole(the internal coordinates within the group are left unchanged). Still otherssimultaneously optimize several internal coordinates specified by the user (e.g., torsional angles (see Torsion Minimization on page 209)).For minimizing residues, see Minimize a Subset of Residues on page 94. SYBYL 8.1Force Fields179Chapter 7. Minimize EnergiesMAXIMIN2 and SimplexThere are several methods to locate the minimum of a function. The methodscan be classified as using no derivatives, using first derivatives only or usingfirst and second derivatives.MAXIMIN2 uses a combination of first and non derivative methods. TheSimplex method [Ref. 53], a non derivative based procedure, is used on an atom by atom basis until the maximum force on any atom is below some specifiedvalue. In highly distorted structures the potential energy surface and its deriva-tives are often discontinuous. Simplex can handle these areas while a derivative based procedure cannot. (Warning: The Simplexing steps may distort rings and invert chiralities.)The primary minimization methods available for use in the MAXIMIN2procedure adjust the atomic coordinates of all the atoms simultaneously basedon the first derivative of the energy equation with respect to the degrees offreedom. Aggregates of atoms, within SYBYL, have no degrees of freedomwhile atoms not in aggregates have three degrees of freedom each (the coordi-nates of the atom). See Minimization Methods below for more details.180Force Fields SYBYL 8.1Chapter 7. Minimize EnergiesMinimizing TutorialSYBYL 8.1Force Fields 1817.1 Minimizing TutorialA Matter of Time: This tutorial requires about 20 minutes personal time andless than 1 minute of run time on a 4 CPU Intel Xeon 3.40GHz.License Requirements: A “BioPolymer” license is required to use the Kollman charges that are specified in the Kollman force field sections of this tutorial.Note about Platforms: Minimization results are sensitive to differences inmathematical rounding on different platforms. The numbers reported in thistutorial were captured on an Linux.This tutorial highlights the general capabilities of SYBYL’s MAXIMIN2minimizer as applied to the small cyclic peptide cyclo-(Gly-Gly-D-Ala-D-Ala-Gly-Gly). The initial conformation of the molecule comes from the published crystal structure (I.L. Karle, J.W. Gibson, J. Karle, J. Amer. Chem. Soc.,92,3755, (1970)).You will also compare a model minimized with the standard force field (Tripos) to the results obtained using two variations of the Kollman force field (all atom and united atom) which were designed especially to handle biopolymers. (See Tripos Force Field on page 142 and Kollman Force Field on page 70 moreinformation on these force fields.)After completing this tutorial, you will be able to:•Set up and run batch calculations using the Tripos force field, the Kollman all atom force field, and Kollman united atom force field.•Compare the Structures by looking at hydrogen bonding patterns. •Compare Conformations using the MATCH option.Ala3Gly2Gly1Gly6Gly5Ala4Chapter 7. Minimize EnergiesMinimizing Tutorial 182Force Fields SYBYL 8.17.1.1 Minimize Using the Tripos Force Field1.Clear the SYBYL screen of all molecules and background images.¾Edit > Clear All 2.Retrieve initial structure from a molecule database.¾File > Open¾Click [$TA_DEMO] in the Bookmarks list, click min_demo.mdb inthe Directory Navigation list, and click PRE_MINIM.mol2 in theSelection list (press OK ). the molecule in M1.¾Edit > Name Molecule ¾Type tripos_ff for the new molecule name (press OK ).4.Specify the force field and type of charges to use.¾Compute > Minimize > Molecule ¾In the Minimize dialog, press Modify .¾In the Energy dialog, select Tripos from the Force Field option menu.¾Select Gasteiger-Huckelfrom the Charges option menu.Chapter 7. Minimize EnergiesMinimizing Tutorial¾Press OK.5.Set the minimization parameters.¾In the Minimize dialog, press Minimize Details.¾In the Minimize Details dialog, increase the maximum number of itera-tions (Max.Iterations) to 1000.¾Decrease the Gradient to 0.005.The Gradient value is a termination criterion. If the gradient differencebetween two consecutive iterations goes below this value, the calculationstops.¾Set the color option to Force.This color codes atoms according to the total force on each atom, as theminimization proceeds.SYBYL 8.1Force Fields183Chapter 7. Minimize EnergiesMinimizing Tutorial 184Force Fields SYBYL 8.1¾Press OK .6.Submit the job to run interactively.¾In the Minimize dialog, type tripos_ffas the job name.Chapter 7. Minimize EnergiesMinimizing Tutorial¾Press OK.As the minimization proceeds, changes to the structure are interactivelydisplayed. Information about each iteration is also printed to the textport.•Energy (kcals/mol)—Total energy.•RMS Force (kcals/mol Å)—Root mean square of all forces resulting from deviation from the ideal for all energy terms. The terminationgradient value (set to 0.005 kcal/mol Å in this tutorial) is the value thatis used to terminate the run (unless the max iterations are reached first).•max Force (kcals/mol Å)—The maximum value in the list of forces determined for each term in the force field equation.•Iteration count—The number of completed iterations.•Eval count—The number of energy evaluations performed.•CPU Time—The amount of CPU time spent on the calculation so far.(The initial “0” is the number of days.)When the calculation completes, information similar to the following appears in the textport:Gradient Convergence reached, terminating.Energy for molecule: tripos_ffBond Stretching Energy : 0.901Angle Bending Energy : 3.848SYBYL 8.1Force Fields185Chapter 7. Minimize EnergiesMinimizing TutorialTorsional Energy : 7.676Out of Plane Bending Energy : 0.2811-4 van der Waals Energy : 3.632van der Waals Energy : -5.0321-4 Electrostatic Energy : 25.619Electrostatic Energy : -45.251===========================Total Energy : -8.327 kcals/molAvg. Number of van der Waals + electrostatic pairs = 852Avg. Number of 1-4 van der Waals + electrostatic pairs = 114Avg. Number of scaled van der Waals + electrostatic pairs = 30Number CPU Time (secs) % of TotalNon Bonded Rebuilds 1 0.00 0.00Energy Evaluations 1532 1.99 100.00Optimization completed, Total Energy : -8.327Total CPU time (secs) = 1.997.Save the molecule to a Mol2 file for later analysis.¾File > Save As¾Enter tripos_ff as the name of the file (press Save).7.1.2 Minimize Using the Kollman All-Atom Force FieldThe Kollman force field has variants, the United Atom and All–Atomapproaches. The SYBYL’s minimization functionality allows the selection ofeither approach or a combination of both. Options are provided to review thehydrogens and charges on the molecule to be sure they are compatible with the model chosen.For this second minimization, the Kollman All–Atom force field is used (S.J.Weiner, P.A. Kollman, D.T. Nguyen, D.A. Case, J. Comp. Chem.,7, 230,1986). This force field has very detailed parametrization for the amino andnucleic acids, including point charges. The charges are loaded from themacromol dictionary.Note: This part of the tutorial requires a “BioPolymer” license.1.Read in the PRE_MINIM structure again and display it in M1. (If min_demo isnot still open, do step 2 of 7.1.1 Minimize Using the Tripos Force Field toreopen the database.)¾Click[$TA_DEMO] in the Bookmarks list, click min_demo.mdb in the Directory Navigation list, and click PRE_MINIM in the Selectionlist.¾Select M1 in the molecule area list (press OK).186Force Fields SYBYL 8.1Chapter 7. Minimize EnergiesMinimizing TutorialSYBYL 8.1Force Fields 187 the molecule.¾Edit > Name Molecule ¾Type koll_all for the new molecule name (press OK ).3.Load Kollman charges onto the molecule.¾Biopolymer > Prepare Structure > Load Charges ¾With m1:koll_all selected in the molecule list, select Kollman All from the Biopolymer pull-down menu (press OK ).4.Specify the force field and charges to use.¾Compute > Minimize > Molecule ¾In the Minimize dialog, press Modify .¾Set the Force Field to Kollman All-Atom .¾Set the Charges to Use Current .5.Adjust the force field options.¾Press Force Field Details .¾In the Force Field Details dialog, enter 1.0 for the One-Four Scaling.¾Make sure the Review of H’s and LP’s check box is turned on .The Review of H’s and LP’s option causes SYBYL to check the hydrogenatoms and add or remove hydrogens based on the Kollman force field optionthat was selected (All or United) prior to minimization.¾Press OK to return to the Energydialog.Chapter 7. Minimize EnergiesMinimizing Tutorial 188Force Fields SYBYL 8.1Note: The only differences between this Energy dialog and the one shownearlier are the Force Field and Charges selections. (Notice also thatCustom appears as the Force Field, even though Kollman All-Atom wasselected. Any time a parameter is changed in the Force Field Details dialog,it is interpreted as customizing the selected force field.)¾Press OK .6.Submit the job.¾In the Minimize dialog, type koll_all as the job name.¾Press OK .7.Save the molecule to a Mol2 file for later analysis.¾File > Save As¾Enter koll_all as the name of the file (press Save ).7.1.3 Minimize Using the Kollman United Atom Force FieldFor this third minimization, use the Kollman United Atom force field (S.J.Weiner, P.A. Kollman, D.A. Case, U.C. Singh, C. Ghio, G. Alagona, S. Profeta,P. Weiner, J. Amer. Chem. Soc.,106, 765, 1984). In this force field, non-polarhydrogens are removed from the structure and only potential H-bondinghydrogens are explicitly considered. The steric loss is compensated for byadjustments to the carbon van der Waals radius.Note:The part of the tutorial requires a “BioPolymer” license.Chapter 7. Minimize EnergiesMinimizing Tutorial1.Rename the structure currently displayed in M1.¾Edit > Name Molecule¾Type koll_uni for the new molecule name (press OK).2.Load Kollman charges onto the molecule.¾Biopolymer > Prepare Structure > Load Charges¾With m1:koll_uni selected in the molecule list, select Kollman Uni from the Biopolymer pull-down menu (press OK).3.Specify force field and charges to use.¾Compute > Minimize > Molecule¾In the Minimize dialog, press Modify.¾In the Energy dialog, set the Force Field option to Kollman United.¾Make sure the Charges option menu is set to Use Current.4.Adjust the force field options.¾Press Force Field Details.¾In the Force Field Details dialog, enter 1.0 for the One-Four Scaling.¾Make sure the Review of H’s and LP’s check box is on (press OK).¾In the Energy dialog, press OK.Note:Custom appears again as the Force Field, even though Kollman United was selected. Since the One-Four Scaling was changed in the Force FieldDetails dialog, it is interpreted as customizing the selected force field.5.Submit the job.¾In the Minimize dialog, type koll_uni as the job name.¾Press OK.Notice that, because the Kollman United force field was selected, onlyhydrogens associated with hydrogen bonding remain on the structure in M1.6.Save the molecule to a Mol2 file.¾File > Save AsSYBYL 8.1Force Fields189Chapter 7. Minimize EnergiesMinimizing Tutorial 190Force Fields SYBYL 8.1¾Enter koll_uni as the name of the file (press Save ).7.1.4 Compare the Structures1.Change the default color coding of the atoms in the molecule to be a singlecolor, depending on the molecule area.¾Options > Tailor¾Select GENERAL as the Subject, then setDEFAULT_COLOR_MODE to BY_SPECTRUM (press Apply , thenClose ).2.Prepare the molecule areas.¾Edit > Delete Molecule(s)¾Click theicon and set the screen to Quartered mode (press Close ).3.Retrieve the results and visually compare the 4 structures:¾File > Open ¾Click [$TA_DEMO] in the Bookmarks list, click min_demo.mdb in the Directory Navigation list, and click PRE_MINIM.mol2 in the Selection list (press OK ).¾File > Open¾With Files of Type set to Molecule , select the following files:-koll_all.mol2-koll_uni.mol2-tripos_ff.mol2¾Press OK .The molecule areas contain the structures colored as follows:•m1 — Original structure in redorange.•m2 — Minimized with Kollman All–Atom force field in user2.•m3 — Minimized with Kollman United–Atom force field in user7.•m4 — Minimized with Tripos force field in user8.The colors will vary depending on your color definitions.Chapter 7. Minimize EnergiesMinimizing Tutorial4.Generate dashed–line hydrogen bonds as background displays for eachmolecule in order to view patterns of hydrogen bonding.¾View > Display H-Bonds > Static¾In the Atom Expression dialog, select M1:PRE_MINIM from the molecule list.¾Press All (press OK).¾Select REDORANGE (press OK).¾Type hbonds1.dsp as the Hbond display filename (press OK).¾Repeat for koll_all, coloring the bonds USER2 and saving them to hbonds2.dsp.¾Repeat for koll_uni, coloring the bonds USER7 and saving them to hbonds3.dsp.¾Repeat for tripos_ff, coloring the bonds USER8 and saving them to hbonds4.dsp.The koll_all molecule (in M2) has a different arrangement of hydrogen bondsthan the other three.7.1.5 Compare ConformationsThe MATCH option can be used to obtain a quantitative measure of thecloseness of 2 conformations of the same molecule. It maps one structure ontoanother by performing a least-squares fit between corresponding atoms in the 2 structures, and reports the quality of the fit.1.Set a Tailor variable to minimize the output from the MATCH option.¾Options > Tailor¾Select MATCH as the Subject.¾Enter5 in the NUM_STD_DEV field.¾Press Apply.2.Set a Tailor variable to show the atom ID when information is listed in thetextport.¾Select GENERAL as the Subject.¾In the ATOM_IDENTIFIER option menu, select IDSYBYL 8.1Force Fields191。