Tutorial Moshe Goldstein Fritz Haber Research Center, Hebrew U. February 13, 2012

Tutorial Plan What is TINKER? Basic Principles of TINKER Operation What can be done with TINKER? mgTINKER - my version of TINKER What can be done with mgTINKER? What cannot be done with TINKER/mgTINKER? Using other packages for/with TINKER Some practice with TINKER and mgTINKER

What is TINKER? TINKER is a Molecular Mechanics package developed at Prof. Jay W. Ponder’s Lab, in the Department of Chemistry at Washington University, in Saint Louis, Missouri, USA.

What is TINKER? TINKER is a set of relatively independent programs written in Fortran. Until version 5, it was written in (sequential) Fortran 77. The latest version 6, written in Fortran 95, supports OpenMP parallelism.

Basic Principles of Operation Molecule Representation XYZ Cartesian Coordinates file includes connectivity and force field-related data SEQ file that includes the amino acids sequence of a peptide or protein PRM file includes force field parameterization data INT Internal Coordinates file includes Z-Matrix and force field-related data

Basic Principles of Operation Cartesian Coordinates Representation

Basic Principles of Operation Internal Coordinates Representation

Basic Principles of Operation Peptide Sequence Files

Basic Principles of Operation Affecting Calculations with a Key Files

Basic Principles of Operation Allowing Continuation of MD with DYN Files

Basic Principles of Operation Kinds of Programs molecule PROGRAM molecule Input Output molecule(s) PROGRAM Calculated value(s) molecule(s) PROGRAM molecule(s) File and/or cmd params Translator/ Constructor File

What can be done with TINKER?

mgTINKER my version of TINKER mgTINKER is a system of relatively independent Python scripts that integrate together one or more TINKER programs. TINKER programs are used as basic “black” boxes, as basic components in order to accomplish more complex computational tasks. The code of several TINKER programs has been changed, and/or combined in order to execute new innovating operators/functions.

mgTINKER my version of TINKER Tinker 3.9 Tinker 4.0 Tinker 4.1 mgTinker Tinker 5.1 Tinker 6.0 Written in Fortran77 Written in Fortran95 + OpenMP Mostly Written in Python

What can be done with mgTINKER? DEEPSAM, an evolutionary protein structure prediction algorithm that integrates together the advantages of the Diffusion Equation Method, Simulated Annealing, L-BFGS and Evolutionary Programming. It was written in Python, and uses existing TINKER programs and also re-written/adapted versions of them.

What can be done with mgTINKER? Several utilities has been written in order to calculate energies and superposition of series of structures calculated by DEEPSAM, and also by minimizations and simulations like MD, MC, SA, DEM, etc.

What cannot be done with TINKER/mgTINKER? One of the most important disadvantages of TINKER is that it does not support non- standard (engineered) amino acids. It is possible to add such a capability, but it requires (a) a lot work in development of additional force field parameters, and (b) a lot of programming work – the Fortran code needs to be expanded to deal with this.

What cannot be done with TINKER/mgTINKER? TINKER supports calculations with implicit solvent models like GBSA, with explicit solvent boxes, in the gas phase, etc., it supports calculations on clusters of water and other kinds of molecules, but it does not support Docking calculations. I am not sure if TINKER supports calculations on complexes of different bio- molecules. I need to check this point.

Using other packages for/with TINKER There exists an API between GAMESS and TINKER that allows QMMM calculations (I have not tried it yet). TINKER programs work as Molecular Mechanics subroutines of GAMESS. There exists a program called Packmol that allows to build an explicit solvent box and put a bio-molecule inside it, generating an file processable by TINKER. …

Some Practice with TINKER and mgTINKER

Tutorial Moshe Goldstein Fritz Haber Research Center, Hebrew U. February 13, 2012 THE END