Molecular modeling tool - TINKER

1. Molecular modeling tool - TINKER Ka-Lok Ng Asia University

2. TINKER • This tool is developed by Prof. Jay Ponder • http://dasher.wustl.edu/ • Download the window version of TINKER (Installation Kit for Windows), install it • Download the user's Guide, read the Force Field Explorer (FFE) web page http://dasher.wustl.edu/ffe/ go to documentation page, read the FFE Manual • Documents are also available at C:\Program Files\TINKER\doc • Open the FFE

3. Description of Force Field Explorer Components Molecular Tree • The Molecular Tree is a structural hierarchy of each system, used for navigating and making selections. When Force Field Explorer opens a structure file, it attempts to groups atoms into protein/nucleic acid macromolecules and their constituent residues. It also groups ions, water and hetero molecules together. This is done even in the absence of a TINKER sequence file. When a display or color command is chosen, all currently selected groups of atoms are affected. • Go to C:\Program Files\TINKER\test, open the enkephalin,xyz file

4. Description of Force Field Explorer Components The first residue of enkephalin has been selected in the Tree view and is highlighted (according to the CPK) model in the graphics window. CPK – after Corey, Pauling and Kultun, N=blue, O=red, C=dark grey, S = yellow, H=light grey

5. Description of Force Field Explorer Components 3D Graphics and Global Axis • Left-clicking the Global Axis, then dragging performs a rotation about the origin of the entire scene. This is useful for manual docking of two systems. • Right-clicking the Global Axis, then dragging performs a translation of the entire scene.

6. Description of Force Field Explorer Components Keyword Editor The Keyword Editor allows modification of keyword files that control various aspects of TINKER calculations. If a Modeling Command is executed on a system, the corresponding Keyword File is automatically saved. Modifications can also be saved at any time using one of the save buttons. Any text or keywords that Force Field Explorer does not recognize are considered “Comments” and are appended to the end of saved key files. As an example, the enkephalin keyword control file is shown below. The Keyword Editor is displaying the enkephalin keyword file.

7. Description of Force Field Explorer Components Modeling Commands The Modeling Commands panel of Force Field Explorer allows launching of most of the TINKER programs. After selecting a routine and configuring its modifying arguments, selecting the “play” button starts the job running. If the routine completes before Force Field Explorer is exited, the textual results in the log file are loaded into the Logs panel. If Force Field Explorer exits while one or more routines are running, they continue in the background unless explicitly killed by the user. The “Optimize” command has been selected for enkephalin

8. Description of Force Field Explorer Components Logs The Logs panel is a simple text editor where output logged from TINKER routines is automatically loaded. It can also be used to edit any text file, for example TINKER coordinate or keyword files. The Log panel shows output logged from a TINKER Optimize command on enkephalin.

9. TINKER example – Anion • Estimation of the free energy of hydration of Cl- anion vs. Br- anion via a 2 picosecond simulation on a "hybrid" anion in a box of water, followed by free energy perturbation • Simulated 1 anion and 214 SPC waters (Simple Point Charge water model) in a cubic Box of side 18.6216 Ang using minimum image periodic boundary conditions. Note the waters are kept rigid and particle mesh Ewald is used for charge interactions (see anion.key file for details) File name and extension anion.key – keywords for the simulation, it contains values for switches and parameters anion.txt – store results for simulation, Atom Type Parameters anion.xyz – Cartesian coord. file for the anions (Cl, Br, unknown) and 214 waters

10. TINKER example – Anion Water - angle bending parameter, K(B)=37.95, angle bond stretching parameter, K(S)=527.2 partial charge of O= -0.82 • anion.key file

11. TINKER example – Anion dynamic anion 1000 2.0 0.1 2 300.0  1000 dynamics steps, interval of the dynamics steps, interval between each coordinate saves (0.1) • Next type archive anion • Answer the questions with Create, use TINKER, 1 20 1  get the anion.arc file

12. TINKER example – Anion Open the anion.arc file with FFE, select the ‘oscillate’ under trajectory, then click the ‘play’ button to see the movie

13. TINKER example – Anion Exercise • Do the same calculation with X replaced by the chloride or bromide anion • Do the calculation with the anion moves to the origin (center) of the box

14. TINKER example – Argon • Performs an initial energy minimization on a periodic box containing 150 argon atoms followed by 6 picoseconds of a molecular dynamics using a modified Beeman integration algorithm and a Bersedsen thermostat. • Steps • Open the argon.xyz • Potential energy programs – under the bin directory, you can copy the archive, minimize, dynamic programs to the example directory • You may need to download the jvm.dll file • Open the DOS console by typing cmd • In the DOS console, type in the following commands, • cp argon.1st argon.xyz • minimize argon 1.0 • dynamic argon 3000 2.0 1.0 4 150.87 49.0

15. TINKER example – Argon • dynamic argon 3000 2.0 1.0 4 150.87 49.0  will generate 6 argon.xxx files • This calculation make use of the MM3 force field parameters (under the TINKER/params directory). Full MM3(2000) parameters including pi-systems. The directional hydrogen bonding and electro-negativity bond length correction terms are implemented. • Next type in ‘archive argon’ • Answer the questions with Create, use TINKER, 1 6 1  get the argon.arc file • Open the argon.arc file with FFE, select the ‘oscillate’ under trajectory, then click the ‘play’ button to see the movie

16. TINKER example - crambin • Generates a TINKER file from a PDB file, followed by a single point energy computation and determination of the molecular volume and surface area • FFE ‘download from PDF’ is not functioning • Use http://www.rcsb.org/pdb/home/home.do, type in the PDB id icrn, save the PDB file to local • Open the DOS console, type in following commands, • pdbxyz 1crn.pdb use the potential parameter file mm3pro.prm  the program will convert a PDB file into a TINKER .xyz Cartesian coordinate file • analyze 1crn.xyz ep -252 255 • spacefill 1crn.xyz 3 1.4 y • The analyze program - allow output of total potential energy of the system, total dipole moment, moments of inertia, radius of gyration, energies associated with specified individual interactions • The spacefill program - compute the volume and surface areas of molecules. • DSSP database - http://www.sander.ebi.ac.uk/dssp/

17. TINKER example - dialanine • Finds all the local minima of alanine dipeptide via a potential energy surface scan through jumping between the minima • A program for general conformational search of an entire potential energy surface via a basin hopping method • type in ‘scan dialanine 0 5 100.0 0.0001’ • type in ‘archive dialanine’  Create  Tinker  1 22 1 • Scan program - A program for general conformational search of an entire potential energy surface via a basin hopping method. before energy minimization after energy minimization

18. TINKER example - formamide • Converts to a unit cell from fractional coordinates, followed by full crystal energy minimization and determination of optimal carbonyl oxygen energy parameters from a fit to lattice energy and structure • crystal formamide.cell 1  generate formamide.xyz • crystal formamide 4 y  generate formamide.xyz_2 • newton formamide a a 0.0001  generate formamide.xyz_3 • xtalfit < formamide.dat