Contents

• Atomistic simulations: an introduction
  • Multiple time steps integration schemes and electrostatic interactions in complex biomolecular systems
  • Enhanced sampling in atomistic simulations
  
  
• Symplectic and Reversible Integrators
  • Canonical Transformation and Symplectic Conditions
  • Liouville Formalism: a Tool for Building Symplectic and Reversible Integrators
  • Potential Subdivision and Multiple Time Steps Integrators for NVE Simulations
  • Constraints and r-RESPA
  • Applications
  
  
• Multiple Time Steps Algorithms for the Isothermal-Isobaric Ensemble
  • The Parrinello-Rahman-Nosé Extended Lagrangian
  • The Parrinello-Rahman-Nosé Hamiltonian and the Equations of Motion
  • Equivalence of Atomic and Molecular Pressure
  • Liouvillean Split and Multiple Time Step Algorithm for the $N{\bf P}T$ Ensemble
  • Group Scaling and Molecular Scaling
  • Switching to Other Ensembles
  
  
• Multiple Time Steps Algorithms For Large Size Flexible Systems with Strong Electrostatic Interactions
  • Subdivision of the ``Bonded'' Potential
  • The smooth particle mesh Ewald method
  • Subdivision the Non Bonded Potential
  • Electrostatic Corrections for the Multiple Time Step Simulation
  
  
• The Hamiltonian Replica Exchange Method
  • Temperature REM
  • Hamiltonian REM
  • Calculating Ensemble Averages Using Configurations from All Ensembles (MBAR estimator)
  
  
• Serial generalized ensemble simulations
  • Introduction
  • Fundamentals of serial generalized-ensemble methods
    • SGE simulations in temperature-space (simulated tempering) and its implementation in the ORAC program
    • SGE simulations in $\lambda$-space
  • The algorithm for optimal weights
    • Tackling free energy estimates
    • Implementation of adaptive free energy estimates in the ORAC program: the BAR-SGE method
    • Free energy evaluation from independent estimates and associated variances
  
  
• Metadynamics Simulation: history-dependent algorithms in Non-Boltzmann sampling
  • Implementation in ORAC 
  
  
• Steered Molecular Dynamics
  • The Crooks theorem
  • Determination of the potential of mean force via bidirectional non equilibrium techniques
  • Implementation in ORAC 
  
  
• Alchemical Transformations
  • Production of the MD trajectory with an externally driven alchemical process
  • Calculation of the alchemical work
  • Fast switching Double Annihilation method
  
  
• Input to ORAC
  • General Features
  • Environments, Commands and Sub-commands
    • &ANALYSIS
    • &INOUT
    • &INTEGRATOR
    • &META
    • &PARAMETERS
    • &POTENTIAL
    • &PROPERTIES
    • &REM
    • &RUN
    • &SETUP
    • &SGE
    • &SIMULATION
    • &SOLUTE
    • &SOLVENT
  • Input to ORAC : Force Field and Topology Files
    • Force Field Parameters
    • Topology
  
  
• Compiling and Running ORAC
  • Compiling the Program
    • Serial version
    • Parallel version
  • How to set dimensions in ORAC : The config.h file
  
  
• Index
• Bibliography

Preface

This manual is for release 6.0 of the program ORAC .^0.1

In release 6.0 ORAC has been equipped with a hybrid Open Multi-Processing(OpenMP)/Message Passing Interface (MPI) multilevel parallelism tailored for generalized ensemble (GE) and fast switching double annihilation (FS-DAM) nonequilibrium (NE) technology[1] for evaluating the binding free energy in drug-receptors system on High Performance Computing platforms. The production of the GE or FS-DAM trajectories is handled using a weak scaling parallel approach on the MPI level only, while a strong scaling force domain decomposition scheme is implemented for intranode computations with shared memory access at the OpenMP level. The present manual is organized as follows: The first seven chapters constitute the ORAC theoretical background. Chapter 1) contains general and introductory remarks. Chapter 2) deals with symplectic and reversible integrators and introduces to the Liouvillean formalism, Chapter 3) extends the Liouvillean formalism to the extended Lagrangian methods and Chapter 4) describes how to deal with long range electrostatic interactions and how to combine the SPME method with the multilevel integration of the equations of motion in order to obtain efficient simulation algorithms. Chapter for 5 to 7 have been added in the release 5. Chapter 5) contains an introduction to replica exchange techniques and a description on how such a technique has been implemented in the ORAC program. Chapter 6) deals with metadynamics simulations. Chapter 7) treats steered molecular dynamics simulation and the theory of non equilibrium processes. Chapter 8) is the command reference of the ORAC program. Chapter 9) contains instructions on how to compile and run ORAC in a serial and parallel environment.

Contributors to ORAC 

Main contributors and license holders:

Piero Procacci^0.2

Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy

E-mail: piero.procacci@unifi.it

Massimo Marchi

Commissariat à l'Énergie Atomique DSV/IBITEC-S/SB2SM Centre d’Études de Saclay, 91191 Gif sur Yvette Cedex, France

E-mail: massimo.marchi@cea.fr

Other contributors:

Simone Marsili

Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy

E-mail: simone.marsili@unifi.it

Role in development: Replica Exchange Method and Metadynamics.

Giorgio Federico Signorini

Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy

E-mail: giorgio.signorini@unifi.it

Role in development: Tests; tools; package, distribution, and version management.

Riccardo Chelli

Dipartimento di Chimica, Università di Firenze, Via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy

E-mail: riccardo.chelli@unifi.it

Role in development: Serial Generalized Ensemble simulations.

Marc Souaille

Medit SA, 2 rue du Belvédère 91120 Palaiseau, France

Role in development: linked cell neighbor listing routines.

Literature citation

The current version of ORAC represents a further development of the release published in 1997[2]. The required citations are

P. Procacci, T. A. Darden, E. Paci, M. Marchi

ORAC: a molecular dynamics program to simulate complex molecular systems with realistic electrostatic interactions

J. Comput. Chem. 1997, Volume:18, Pages:1848-1862

S. Marsili, G. F. Signorini, R. Chelli, M. Marchi, P. Procacci

ORAC: a molecular dynamics simulation program to explore free energy surfaces in biomolecular systems at the atomistic level

J. Comput. Chem. 2010, Volume:31, Pages:1106-1116

In general, in addition to the above citations, we recommend citing the original references describing the theoretical methods used when reporting results obtained from ORAC calculations. These references are given in the description of the theory through the user guide as well as in the description of the relevant keywords.