TINKER Tools for Molecular Design Version 8.9 June 2021 Copyright © 1990-2021 by Jay William Ponder All Rights Reserved User's Guide Cover Illustration by Jay Nelson Courtesy of Prof. R. T. Paine, Univ. of New Mexico TINKER IS PROVIDED "AS IS" AND WITHOUT ANY WARRANTY EXPRESS OR IMPLIED. THE USER ASSUMES ALL RISKS OF USING THIS SOFTWARE. THERE IS NO CLAIM OF THE MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. YOU MAY MAKE COPIES OF TINKER FOR YOUR OWN PERSONAL, ACADEMIC OR NONPROFIT USE, AND YOU MAY MODIFY THOSE COPIES. YOU MAY NOT DISTRIBUTE ANY ORIGINAL OR MODIFIED SOURCE CODE, EXECUTABLES OR DOCUMENTATION TO USERS AT ANY SITE OTHER THAN YOUR OWN. PLEASE READ THE FULL TINKER LICENSE, AND SIGN AND RETURN THE LICENSE AGREEMENT IF YOU MAKE USE OF THIS SOFTWARE. COMMERCIAL USE OF TINKER IS GOVERNED UNDER A SEPARATE AGREEMENT AS DESCRIBED IN THE FULL TINKER LICENSE. V8.9 06/21 Tinker User's Guide TinkerTools Organization Jul 21, 2021 CONTENTS 1 Introduction to the Software 1 1.1 What is Tinker? ...................................... 1 1.2 Features and Capabilities ................................. 1 1.3 Contact Information .................................... 3 2 Installation on Your Computer 5 2.1 How to Obtain a Copy of Tinker ............................. 5 2.2 Prebuilt Tinker Executables ................................ 5 2.3 Building your Own Executables .............................. 5 2.4 Tinker-FFE (Force Field Explorer) ............................ 6 2.5 Documentation and Other Information .......................... 7 2.6 Where to Direct Questions ................................ 7 3 Types of Input & Output Files 9 4 Potential Energy Programs 13 5 Analysis & Utility Programs & Scripts 21 6 Force Field Parameter Sets 27 7 Special Features & Methods 35 7.1 File Version Numbers ................................... 35 7.2 Command Line Options .................................. 36 7.3 Use on Windows Systems ................................. 36 7.4 Use on MacOS Systems .................................. 37 7.5 Atom Types vs. Atom Classes ............................... 37 7.6 Calculations on Partial Structures ............................. 38 7.7 Metal Complexes and Hypervalent Species ....................... 38 7.8 Neighbor Methods for Nonbonded Terms ........................ 39 7.9 Periodic Boundary Conditions ............................... 39 7.10 Distance Cutoffs for Energy Functions .......................... 39 7.11 Ewald Summations Methods ............................... 39 7.12 Continuum Solvation Models ............................... 40 7.13 Polarizable Multipole Electrostatics ............................ 40 7.14 Potential Energy Smoothing ................................ 41 i 7.15 Distance Geometry Metrization .............................. 41 8 Use of the Keyword Control File 43 8.1 Using Keywords to Control Tinker Calculations ..................... 43 8.2 Keywords Grouped by Functionality ........................... 44 8.3 Description of Individual Keywords ............................ 48 9 Routines & Functions 91 10 Modules & Global Variables 179 11 Test Cases & Examples 221 12 Benchmark Results 225 12.1 Calmodulin Energy Evaluation (Serial) .........................225 12.2 Crambin Crystal Energy Evaluation (Serial) .......................225 12.3 Crambin Normal Mode Calculation (Serial) .......................226 12.4 Water Box Molecular Dynamics using TIP3P (Serial) ..................226 12.5 Water Box Molecular Dynamics using AMOEBA (Serial) ................226 12.6 MD on DHFR in Water using CHARMM (OpenMP Parallel) ..............227 12.7 MD on DHFR in Water using AMOEBA (OpenMP Parallel) ...............227 12.8 MD on COX-2 in Water using OPLS-AA (OpenMP Parallel) ...............228 12.9 MD on COX-2 in Water using AMOEBA (OpenMP Parallel) ...............228 13 Acknowledgments 231 14 References 235 14.1 Molecular Mechanics & Dynamics Software Packages ..................235 14.2 Literature References by Topic ..............................241 Index 255 ii CHAPTER ONE INTRODUCTION TO THE SOFTWARE 1.1 What is Tinker? Welcome to the Tinker molecular modeling package! Tinker is designed to be an easily used and flexible system of programs and routines for molecular mechanics and dynamics as well as other energy-based and structural manipulation calculations. It is intended to be modular enough to enable development of new computational methods and efficient enough to meet most production calculation needs. Rather than incorporating all the functionality in one monolithic program, Tin- ker provides a set of relatively small programs that interoperate to perform complex computations. New programs can be easily added by modelers with only limited programming experience. 1.2 Features and Capabilities The series of major programs included in the distribution system perform the following core tasks: (1) building protein and nucleic acid models from sequence (2) energy minimization and structural optimization (3) analysis of energy distribution within a structure (4) molecular dynamics and stochastic dynamics (5) simulated annealing with a choice of cooling schedules (6) normal modes and vibrational frequencies (7) conformational search and global optimization (8) transition state location and conformational pathways (9) fitting of energy parameters to crystal data (10) distance geometry with pairwise metrization (11) molecular volumes and surface areas (12) free energy changes for structural mutations (13) advanced algorithms based on potential smoothing 1 Tinker User's Guide Many of the various energy minimization and molecular dynamics computations can be performed on full or partial structures, over Cartesian, internal or rigid body coordinates, and including a variety of boundary conditions and crystal cell types. Other programs are available to generate timing data and allow checking of potential function derivatives for coding errors. Special features are available to facilitate input and output of protein and nucleic acid structures. However, the basic core routines have no knowledge of biopolymer structure and can be used for general molecular systems. Due to its emphasis on ease of modification, Tinker differs from many other currently available molecular modeling packages in that the user is expected to be willing to write simple “front-end” programs and make some alterations at the source code level. The main programs provided should be considered as templates for the users to change according to their wishes. All subroutines are internally documented and structured programming practices are adhered to throughout. The result, it is hoped, will be a calculational system which can be tailored to local needs and desires. The core Tinker system consists of over 240,000 lines of source written entirely in a portable Fortran superset. Use is made of only some very common extensions that aid in writing highly structured code. The current version of the package has been ported to a wide range of computers with no or extremely minimal changes. Tested systems include: Ubuntu, CentOS and Red Hat Linux, Microsoft Windows 10 and earlier, Apple MacOS, and various older Unix-based workstations under vendor supplied Unix. At present, our new code is written on various Linux platforms, and occasionally tested for compatibility on various of the other machine and OS combinations listed above. At present, our primary source code development efforts are in Fortran, using a portable subset of Fortran90 with some common extensions. A machine-translated C version of Tinker is currently available, and a hand-translated optimized C version of a previous Tinker release is available for inspection. Conversion to C or C++ is under consideration, but not being actively pursued at this time. The basic design of the energy function engine used by the Tinker system allows usage of several different parameter sets. At present we are distributing parameters that implement several Am- ber and CHARMM potentials, MM2, MM3, OPLS-UA, OPLS-AA, MMFF, Liam Dang’s polarizable potentials, and our own AMOEBA (Atomic Multipole Optimized Energetics for Biomolecular Appli- cations), AMOEBA+, and HIPPO (Hydrogen-like Intermolecular Polarizable Potential) force fields. In most cases, the source code separates the geometric manipulations needed for energy derivatives from the actual form of the energy function itself. Several other literature parameter sets are be- ing considered for possible future development (later versions of CHARMM and Amber, as well as GROMOS, ENCAD, MM4, UFF, etc.), and many of the alternative potential function forms reported in the literature can be implemented directly or after minor code changes. Much of the software in the Tinker package has been heavily used and well tested, but some mod- ules are still in a fairly early stage of development. Further work on the Tinker system is planned in three main areas: (1) extension and improvement of the potential energy parameters includ- ing additional parameterization and testing of our polarizable multipole AMOEBA force field, (2) coding of new computational algorithms including additional methods for free energy determina- tion, torsional Monte Carlo and molecular dynamics sampling, advanced methods for long range interactions, better transition state location, and further application of the potential smoothing paradigm, and (3) further development of Force Field Explorer, a Java-based GUI front-end to the Tinker programs that provides for calculation setup, launch and control