Amber 2021 Reference Manual (Covers Amber20 and AmberTools21) Amber 2021 Reference Manual (Covers Amber20 and AmberTools21) Principal contributors to the current codes: David A. Case (Rutgers) Robert E. Duke (UNT) Ross C. Walker (UC San Diego, GSK) Nikolai R. Skrynnikov (Purdue, SPbU) Thomas E. Cheatham III (Utah) Oleg Mikhailovskii (Purdue, SPbU) Carlos Simmerling (Stony Brook) Yi Xue (Tsinghua) Adrian Roitberg (Florida) Sergei A. Izmailov (SPbU) Kenneth M. Merz (Michigan State) Koushik Kasavajhala (Stony Brook) Ray Luo (UC Irvine) Kellon Belfon (Stony Brook) Pengfei Li (Yale, Loyola) Jana Shen (Maryland) Tom Darden (OpenEye) Robert Harris (Maryland) Celeste Sagui (NCSU) Alexey Onufriev (Virginia Tech) Feng Pan (FSU) Saeed Izadi (Virginia Tech, Genentech) Junmei Wang (Pitt) Xiongwu Wu (NIH) Daniel R. Roe (NIH) Holger Gohlke (Düsseldorf/FZ Jülich) Scott LeGrand (NVIDIA) Stephan Schott-Verdugo (FZ Jülich) Jason Swails (Lutron) Ruxi Qi (UC Irvine) Andreas W. Götz (UC San Diego) Haixin Wei (UC Irvine) Jamie Smith (USC) Shiji Zhao (UC Irvine) David Cerutti (Rutgers) Edward King (UC Irvine) Taisung Lee (Rutgers) George Giambasu (Rutgers) Darrin York (Rutgers) Jian Liu (Peking Univ.) Tyler Luchko (CSU Northridge) Hai Nguyen (Rutgers) Viet Man (Pitt) Scott R. Brozell (Rutgers) Vinícius Wilian D. Cruzeiro (UC San Diego) Andriy Kovalenko (NINT) Gérald Monard (U. Lorraine) Mike Gilson (UC San Diego) Yinglong Miao (Kansas) Ido Ben-Shalom (UC San Diego) Jinan Wang (Kansas) Tom Kurtzman (CUNY) Romain M. Wolf (Bangkok, Thailand) Sergio Pantano (Inst. Pasteur, Uruguay) Charles Lin (Silicon Therapeutics) Matias Machado (Inst. Pasteur, Uruguay) G. Andrés Cisneros (UNT) H. Metin Aktulga (Michigan State) Ali Rahnamoun (Michigan State) Mehmet Cagri Kaymak (Michigan State) Chi Jin (Michigan State) Kurt A. O’Hearn (Michigan State) Madushanka Manathunga (Michigan State) Peter A. Kollman (UC San Francisco) For more information, please visit https://ambermd.org/contributors.html 3 • When citing Amber 2021 (comprised of AmberTools21 and Amber20) in the literature, the following citation should be used: D.A. Case, H.M. Aktulga, K. Belfon, I.Y. Ben-Shalom, S.R. Brozell, D.S. Cerutti, T.E. Cheatham, III, G.A. Cisneros, V.W.D. Cruzeiro, T.A. Darden, R.E. Duke, G. Giambasu, M.K. Gilson, H. Gohlke, A.W. Goetz, R. Harris, S. Izadi, S.A. Izmailov, C. Jin, K. Kasavajhala, M.C. Kaymak, E. King, A. Kovalenko, T. Kurtzman, T.S. Lee, S. LeGrand, P. Li, C. Lin, J. Liu, T. Luchko, R. Luo, M. Machado, V. Man, M. Manathunga, K.M. Merz, Y. Miao, O. Mikhailovskii, G. Monard, H. Nguyen, K.A. O’Hearn, A. Onufriev, F. Pan, S. Pantano, R. Qi, A. Rahnamoun, D.R. Roe, A. Roitberg, C. Sagui, S. Schott-Verdugo, J. Shen, C.L. Simmerling, N.R. Skrynnikov, J. Smith, J. Swails, R.C. Walker, J. Wang, H. Wei, R.M. Wolf, X. Wu, Y. Xue, D.M. York, S. Zhao, and P.A. Kollman (2021), Amber 2021, University of California, San Francisco. • Peter Kollman died unexpectedly in May, 2001. We dedicate Amber to his memory. • Cover illustration: Complex lipid bilayer and membrane-protein/lipid bilayer systems generated with Packmol- Memgen. See J. Chem. Inf. Model., 59, 2522-2528 (2019). Illustration created by Stephan Schott-Verdugo . 4 Contents Contents 5 I. Introduction and Installation 13 1. Introduction 15 1.1. Information flow in Amber...................................... 15 1.2. List of programs............................................ 18 2. Installation 23 2.1. Basic installation guide........................................ 23 2.2. The cmake build system in Amber.................................. 25 2.3. Python in Amber........................................... 30 2.4. Applying Updates........................................... 31 2.5. Contacting the developers....................................... 33 II. Amber force fields 35 3. Molecular mechanics force fields 37 3.1. Proteins................................................ 38 3.2. Nucleic acids............................................. 43 3.3. Carbohydrates............................................. 45 3.4. Lipids................................................. 52 3.5. Solvents................................................ 54 3.6. Ions.................................................. 56 3.7. Modified amino acids and nucleotides................................ 58 3.8. Force fields related to semi-empirical QM.............................. 59 3.9. The GAL17 force field for water over platinum........................... 59 3.10. Fluorescent dyes: AMBER-DYES in AMBER force field files................... 60 3.11. Coarse-grained and multiscale simulations using the SIRAH force field.............. 62 3.12. Obsolete force field files....................................... 65 4. The Generalized Born/Surface Area Model 69 4.1. GB/SA input parameters....................................... 71 4.2. ALPB (Analytical Linearized Poisson-Boltzmann)......................... 74 5. GBNSR6 77 5.1. GB equations available in gbnsr6................................... 77 5.2. Numerical implementation of the R6 integral............................ 77 5.3. Usage................................................. 78 6. PBSA 81 6.1. Introduction.............................................. 81 6.2. Usage and keywords......................................... 84 6.3. Example inputs and demonstrations of functionalities........................ 92 5 CONTENTS 6.4. Visualization functions in pbsa .................................... 95 6.5. pbsa in sander and NAB....................................... 102 6.6. GPU accelerated pbsa ......................................... 104 7. Reference Interaction Site Model 108 7.1. Introduction.............................................. 108 7.2. Practical Considerations....................................... 114 7.3. Work Flow.............................................. 117 7.4. rism1d................................................. 119 7.5. 3D-RISM in NAB ........................................... 122 7.6. rism3d.snglpnt ........................................... 124 7.7. 3D-RISM in sander.......................................... 128 7.8. RISM File Formats.......................................... 138 8. Empirical Valence Bond 144 8.1. Introduction.............................................. 144 8.2. General usage description....................................... 145 8.3. Biased sampling............................................ 147 9. sqm: Semi-empirical quantum chemistry 150 9.1. Available Hamiltonians........................................ 150 9.2. Dispersion and hydrogen bond correction.............................. 152 9.3. Usage................................................. 153 10. QUICK: ab initio quantum chemistry 159 10.1. Features and limitations........................................ 159 10.2. Installation.............................................. 160 10.3. Usage................................................. 160 11. QM/MM calculations 162 11.1. Built-in semiempirical NDDO methods and SCC-DFTB...................... 162 11.2. Interface for ab initio and DFT methods............................... 171 11.3. QM/MM simulations with QUICK.................................. 188 11.4. Adaptive solvent QM/MM simulations................................ 190 11.5. Adaptive buffered force-mixing QM/MM.............................. 195 11.6. SEBOMD: SemiEmpirical Born-Oppenheimer Molecular Dynamics................ 202 11.7. ReaxFF/AMBER........................................... 207 12. Using energies and forces from an external library 212 12.1. Installation instructions........................................ 212 12.2. Simulation setup and input parameters................................ 212 III. System preparation 213 13. Preparing PDB Files 215 13.1. Cleaning up Protein PDB Files for AMBER............................. 215 13.2. Residue naming conventions..................................... 216 13.3. Chains, Residue Numbering, Missing Residues........................... 217 13.4. pdb4amber.............................................. 217 13.5. reduce................................................. 219 13.6. packmol-memgen........................................... 220 13.7. Building bilayer systems with AMBAT................................ 224 6 CONTENTS 14. LEaP 226 14.1. Introduction.............................................. 226 14.2. Concepts............................................... 226 14.3. Running LEaP............................................. 230 14.4. Basic instructions for using LEaP to build molecules........................ 235 14.5. Error Handling and Reporting.................................... 236 14.6. Commands.............................................. 236 14.7. Building oligosaccharides, lipids and glycoproteins......................... 254 15. Reading and modifying Amber parameter files 263 15.1. Understanding Amber parameter files................................ 263 15.2. ParmEd................................................ 271 16. Antechamber and GAFF 300 16.1. Principal programs.......................................... 300 16.2. A simple example for antechamber.................................. 305 16.3. Programs called by antechamber................................... 308 16.4. Miscellaneous programs....................................... 311 17. Molecular Mechanics Parameter Fitting in mdgx 315 17.1. Input and Output........................................... 315 17.2. Installation.............................................. 316 17.3. Partial Charge