Amber 2020

1 Amber 2020. Reference Manual (Covers Amber20 and AmberTools20). Principal contributors to the current codes: David A. Case (Rutgers) G. Andr s Cisneros (UNT). Ross C. Walker (UCSD, GSK) Robert E. Duke (UNT). Thomas E. Cheatham III (Utah) Nikolai R. Skrynnikov (Purdue, SPbU). Carlos Simmerling (Stony Brook) Oleg Mikhailovskii (Purdue, SPbU). Adrian Roitberg (Florida) Yi Xue (Tsinghua). Kenneth M. Merz (Michigan State) Sergei A. Izmailov (SPbU). Pengfei Li (Yale) Koushik Kasavajhala (Stony Brook). Ray Luo (UC Irvine) Kellon Belfon (Stony Brook). Tom Darden (OpenEye) Jana Shen (Maryland). Celeste Sagui (NCSU) Robert Harris (Maryland). Feng Pan (FSU) Charles Lin (Silicon Therapeutics). Junmei Wang (Pitt) Alexey Onufriev (Virginia Tech). Daniel R. Roe (NIH) Saeed Izadi (Virginia Tech, Genentech). Scott LeGrand (NVIDIA) Yeyue Xiong (Virginia Tech). Jason Swails (Lutron) Romain M. Wolf (Bangkok, Thailand). Andreas W. G tz (UCSD) Xiongwu Wu (NIH).

2 Jamie Smith (USC) Holger Gohlke (D sseldorf). David Cerutti (Rutgers) Stephan Schott-Verdugo (D sseldorf). Taisung Lee (Rutgers) Ruxi Qi (UC Irvine). Darrin York (Rutgers) George Giambasu (Rutgers). Tyler Luchko (CSU Northridge) Jian Liu (Peking Univ.). Leighton Wilson (Michigan) Hai Nguyen (Rutgers). Robert Krasny (Michigan) Scott R. Brozell (Rutgers). Viet Man (Pitt) Andriy Kovalenko (NINT). Vin cius Wilian D. Cruzeiro (UCSD) Mike Gilson (UCSD). G rald Monard (U. Lorraine) Ido Ben-Shalom (UCSD). Yinglong Miao (Kansas) Tom Kurtzman (CUNY). Jinan Wang (Kansas) Sergio Pantano (Inst. Pasteur, Uruguay). Peter A. Kollman (UC San Francisco). For more information, please visit 3. When citing Amber 2020 (comprised of AmberTools20 and Amber20) in the literature, the following citation should be used: Case, K. Belfon, Ben-Shalom, Brozell, Cerutti, Cheatham, III, Cruzeiro, Darden, Duke, G. Giambasu, Gilson, H. Gohlke, Goetz,R Harris, S.

3 Izadi, Iz- mailov, K. Kasavajhala, A. Kovalenko, R. Krasny, T. Kurtzman, Lee, S. LeGrand, P. Li, C. Lin, J. Liu, T. Luchko, R. Luo, V. Man, Merz, Y. Miao, O. Mikhailovskii, G. Monard, H. Nguyen, A. Onufriev, F. Pan, S. Pantano, R. Qi, Roe, A. Roitberg, C. Sagui, S. Schott-Verdugo, J. Shen, Simmerling, Skrynnikov, J. Smith, J. Swails, Walker, J. Wang, L. Wilson, Wolf, X. Wu, Y. Xiong, Y. Xue, York and Kollman (2020), Amber 2020, University of California, San Francisco. Peter Kollman died unexpectedly in May, 2001. We dedicate Amber to his memory. Cover illustration: representation of cytochrome c3 being studied using simulations at constant pH and constant redox potential in Amber , using methodology developed by Adrian Roitberg's group. Multiple examples are given in J. Am. Chem. Soc. 142, 3823-3835 (2020). Figure by Vin cius Wilian D. Cruzeiro. 4. Contents Contents 5. I. Introduction and Installation 11. 1. Introduction 13.

4 Information flow in Amber .. 13. List of programs .. 16. 2. Installation 21. Basic installation guide .. 21. The cmake build system in Amber .. 23. Python in Amber .. 28. Applying Updates .. 28. Installation using the old (legacy) build system .. 31. Contacting the developers .. 32. II. Amber force fields 33. 3. Molecular mechanics force fields 35. Proteins .. 36. Nucleic acids .. 41. Carbohydrates .. 43. Lipids .. 50. Solvents .. 52. Ions .. 54. Modified amino acids and nucleotides .. 56. Force fields related to semi-empirical QM .. 57. The GAL17 force field for water over platinum .. 57. Fluorescent dyes: Amber -DYES in Amber force field files .. 58. Coarse-grained and multiscale simulations using the SIRAH force field .. 60. Obsolete force field files .. 62. 4. The Generalized Born/Surface Area Model 67. GB/SA input parameters .. 69. ALPB (Analytical Linearized Poisson-Boltzmann) .. 72. 5. GBNSR6 75. GB equations available in gbnsr6.

5 75. Numerical implementation of the R6 integral .. 75. Usage .. 76. 6. PBSA 79. Introduction .. 79. Usage and keywords .. 82. 5. CONTENTS. Example inputs and demonstrations of functionalities .. 90. Visualization functions in pbsa .. 93. pbsa in sander and NAB .. 100. GPU accelerated pbsa .. 102. 7. Reference Interaction Site Model 105. Introduction .. 105. Practical Considerations .. 111. Work Flow .. 114. rism1d .. 116. 3D-RISM in NAB .. 119.. 121. 3D-RISM in sander .. 125. RISM File Formats .. 135. 8. Empirical Valence Bond 141. Introduction .. 141. General usage description .. 142. Biased sampling .. 144. 9. sqm: Semi-empirical quantum chemistry 147. Available Hamiltonians .. 147. Dispersion and hydrogen bond correction .. 149. Usage .. 150. 10. QM/MM calculations 156. Built-in semiempirical NDDO methods and SCC-DFTB .. 156. Interface for ab initio and DFT methods .. 165. Adaptive solvent QM/MM simulations .. 182.

6 Adaptive buffered force-mixing QM/MM .. 187. SEBOMD: SemiEmpirical Born-Oppenheimer Molecular Dynamics .. 194. 11. Using energies and forces from an external library 199. Installation instructions .. 199. Simulation setup and input parameters .. 199. III. System preparation 201. 12. Preparing PDB Files 203. Cleaning up Protein PDB Files for Amber .. 203. Residue naming conventions .. 204. Chains, Residue Numbering, Missing Residues .. 205. pdb4amber .. 205. reduce .. 207. packmol-memgen .. 208. Building bilayer systems with AMBAT .. 212. 13. LEaP 213. Introduction .. 213. Concepts .. 213. Running LEaP .. 217. Basic instructions for using LEaP to build molecules .. 222. Error Handling and Reporting .. 223. 6. CONTENTS. Commands .. 223. Building oligosaccharides, lipids and glycoproteins .. 240. 14. Reading and modifying Amber parameter files 249. Understanding Amber parameter files .. 249. ParmEd .. 257. 15. Antechamber and GAFF 286.

7 Principal programs .. 286. A simple example for antechamber .. 291. Programs called by antechamber .. 294. Miscellaneous programs .. 297. 16. Molecular Mechanics Parameter Fitting in mdgx 301. Input and Output .. 301. Installation .. 302. Partial Charge Development .. 302. Implicitly Polarized Charge Development .. 304. Customizable Virtual Site Support .. 306. Bonded Term Fitting in mdgx .. 309. Configuration Sampling .. 312. Parallel Generalized Born Problems on the GPU .. 315. 17. Python Metal Site Modeling Toolbox (pyMSMT) 317. Introduction .. 317. Usage .. 318. 18. Setting up crystal simulations 331. UnitCell .. 331. PropPDB .. 331. AddToBox .. 332. ChBox .. 333. IV. Running simulations 334. 19. sander 336. Introduction .. 336. File usage .. 337. Example input files .. 338. Namelist Input Syntax .. 339. Overview of the information in the input file .. 340. General minimization and dynamics parameters .. 340. Potential function parameters.

8 359. Varying conditions .. 367. File redirection commands .. 371. debugging information .. 371. (and multipmemd) .. 374. as an alternate PB solver in Sander .. 375. 's Corner: The sander API .. 377. 20. pmemd 398. Introduction .. 398. Functionality .. 398. 7. CONTENTS. PMEMD-specific namelist variables .. 400. Slightly changed functionality .. 401. Parallel performance tuning and hints .. 402. GPU Accelerated PMEMD .. 403. 21. Atom and Residue Selections 410. Amber Masks .. 410. "Atom Expressions" in NAB Applications .. 413. GROUP Specification .. 413. 22. Sampling configuration space 418. Self-Guided Langevin dynamics .. 418. Accelerated Molecular Dynamics .. 421. Gaussian Accelerated Molecular Dynamics .. 424. Targeted MD .. 430. Multiply-Targeted MD (MTMD) .. 431. Nudged elastic band calculations .. 433. Low-MODe (LMOD) methods .. 436. 23. Free energies 441. Thermodynamic integration .. 441. Linear Interaction Energies.

9 455. Replica Exchange Molecular Dynamics (REMD) .. 455. Adaptively Biased MD, Steered MD, Umbrella Sampling with REMD and String Method .. 480. Steered Molecular Dynamics (SMD) and the Jarzynski Relationship .. 496. Absolute Free Energies using EMIL .. 498. 24. Constant pH calculations 510. Background .. 510. Preparing a system for constant pH simulation .. 510. Running at constant pH .. 513. Analyzing constant pH simulations .. 516. Extending constant pH to additional titratable groups .. 516. pH Replica Exchange MD .. 521. cphstats .. 521. 25. Constant Redox Potential calculations 530. Preparing a system for constant Redox Potential simulation .. 530. Running at constant Redox Potential .. 532. Analyzing constant Redox Potential simulations .. 533. Extending constant Redox Potential to additional titratable groups .. 533. Redox Potential Replica Exchange MD .. 533. cestats .. 534. 26. Continuous constant pH molecular dynamics 537.

10 Implementation notes .. 537. Usage description .. 538. Continuous constant pH MD with pH replica exchange .. 542. Obtaining parameters for a novel titratable group .. 544. 27. NMR refinement 545. Distance, angle and torsional restraints .. 546. NOESY volume restraints .. 551. Chemical shift restraints .. 552. 8. CONTENTS. Pseudocontact shift restraints .. 553. Direct dipolar coupling restraints .. 555. Residual CSA or pseudo-CSA restraints .. 557. Preparing restraint files for Sander .. 557. Getting summaries of NMR violations .. 564. Time-averaged restraints .. 565. copies refinement using LES .. 566. sample input files .. 566. 28. Xray and cryoEM refinement 571. EMAP restraints for rigid and flexible fitting into EM maps .. 571. FRET rest: F rster Resonance Energy Transfer restraints .. 572. X-ray functionality and diffraction-based restraints for pmemd .. 574. 29. Locally-enchanced sampling 577. Preparing to use LES with Amber .