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                 TINKER -- Software Tools for Molecular Design
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                    Jay Ponder Lab, Department of Chemistry,
           Washington University, Saint Louis, Missouri 63130 U.S.A.

     TINKER is a complete package for performing empirical force field
molecular mechanics and dynamics calculations. It is intended to serve as a
platform for algorithm development and parameterization, while still being
efficient enough for most production work. Available potentials include Amber
ff94, ff96, ff98 and ff99, ff99sb, CHARMM19, CHARMM22/CMAP, DANG, MM2, MM3,
MMFF, OPLS-UA, OPLS-AA and our AMOEBA 2004 and 2009 polarizable atomic
multipole models. Other force fields can be added via new parameter files,
and some are currently under consideration.

     Programs are provided to perform many functions including: (1) energy
minimization over Cartesian coordinates, torsional angles or rigid bodies
via conjugate gradient, variable metric or our truncated Newton method, (2)
molecular, stochastic and rigid body dynamics with periodic boundaries and
control of temperature and pressure, (3) multiple time step RESPA integrator
for more efficient MD simulation, (4) normal mode vibrational analysis, (5)
distance geometry including an efficient random pairwise metrization, (6)
building protein and nucleic acid structures from sequence, (7) analysis
and breakdown of single point potential energies, (8) verification of
analytical derivatives of standard and user defined potentials, (9) location
of a transition state between two minima, (10) full energy surface search via
our Conformation Scanning method, (11) free energy calculations via free energy
perturbation or weighted histogram analysis, (12) analysis of and comparison
to electrostatic potentials, (13) fitting of intermolecular potential
parameters to structural and thermodynamic data, and (14) global optimization
via simulated annealing, Monte Carlo minimization, and energy surface
smoothing via the Potential Smoothing and Search (PSS) method.

     Analytical Cartesian derivatives through the Hessian and analytical
torsional gradients are available. Energy minimization and vibrational analysis
can be performed in either Cartesian or torsional space. The user can define
rigid bodies and compute scaled energies between or within bodies. Atomic
multipoles through the quadrupole and induced dipole polarization, as well as
simpler electrostatic models, are implemented. Restraint potentials may be
included in all calculation types, and partial structures can be frozen in
space. Both replicative and image boundary conditions are supported for all
unit cell types and for truncated octahedra. Nonbonded interactions can be
splined over distance windows, and are treated via double loop search, the
Method of Lights, or pair neighbor lists. Particle mesh Ewald (PME) is
available for partial charges and for polarizable atomic multipoles. The
molecular volume and surface area as well as their derivatives are included.
Various continuum solvation models, such as GB/SA, GK and PB, are implemented.
User-defined potentials are easily added.

     The heart of the TINKER package is a modular set of callable routines
which allow the manipulation of coordinates and evaluation of potential energy
and derivatives in a straightforward fashion. The author welcomes development
by others of new modules for TINKER and is willing to serve as a resource and
distribution center for such development efforts.

     A complete Java GUI for TINKER, call Force Field Explorer or FFE, is
available as an adjunct to the basic package. FFE is tightly integrated with
the TINKER code via a socket mechanism, and can be used to setup, launch and
visualize TINKER calculations. The GUI allows for interactive use on a single
machine, as well as connection to jobs running on a remote server.

     The TINKER package is written in a portable Fortran 95 dialect that
makes use of dynamid memory allocation. TINKER uses OpenMP to parallelize
selected CPU intensive calculations on shared-memory multiple core systems.
Program control is via an optional Keyword Parameter. Auxiliary programs are
provided to convert Protein Data Bank files to and from the TINKER formats.
TINKER coordinate files are directly supported by the VMD, PyMOL and MOLDEN
modeling packages. TINKER structures are also compatible with the ChemDraw &
ChemOffice programs.

Selected References:

1. Polarizable Atomic Multipole-based Molecular Mechanics for Organic
   Molecules, P. Ren, C. Wu and J. W. Ponder, J. Chem. Theory Comput.,
   7, 3143-3461 (2011).

2. Current Status of the AMOEBA Polarizable Force Field, J. W. Ponder, C. Wu,
   P. Ren, V. S. Pande, J. D. Chodera, D. L. Mobley, M. J. Schnieders,
   I. Haque, D. S. Lambrecht, R. A. DiStatio, Jr., M. Head-Gordon,
   G. N. I. Clark, M. E. Johnson and T. Head-Gordon, J. Phys. Chem. B, 114,
   2549-2564 (2010).

3. Polarizable Atomic Multipole Water Model for Molecular Mechanics
   Simulation, P. Ren and J. W. Ponder, J. Phys. Chem. B, 107, 5933-5947
   (2003).

4. Analysis and Application of Potential Energy Smoothing for Global
   Optimization, R. V. Pappu, R. K. Hart and J. W. Ponder, J. Phys. Chem. B,
   102, 9725-9742 (1998).

5. Reaction Field Methods for Off-Center Multipoles, Y. Kong and
   J. W. Ponder, J. Chem. Phys., 107, 481-492 (1997).

6. Algorithms for Calculating Excluded Volume and Its Derivatives as a
   Function of Molecular Conformation and Their Use in Energy Minimization,
   C. E. Kundrot, J. W. Ponder and F. M. Richards, J. Comput. Chem., 12,
   402-409 (1991).

7. An Efficient Newton-like Method for Molecular Mechanics Energy Minimization
   of Large Molecules, J. W. Ponder and F. M. Richards, J. Comput. Chem., 8,
   1016-1024 (1987).

Availability:   Executables and Source at http://dasher.wustl.edu/tinker/
Version:        TINKER 6.2 and Force Field Explorer 6.0 of February 2013
Language:       Fortran 95 with common extensions and some C;
                FFE GUI in Java with Java 3D extensions
Lines of Code:  196,000 in TINKER Package (Fortran 95 and some C)
                30,000 in Force Field Explorer (Java and some C)
