
                 ---------------------------------------------
                 TINKER -- Software Tools for Molecular Design
                 ---------------------------------------------

      Jay Ponder Lab, Department of Biochemistry and Molecular Biophysics,
  Washington University School of Medicine, Saint Louis, Missouri 63110 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. The available potentials include
Amber ff94, ff96, ff98 and ff99, CHARMM19, CHARMM27, DANG, MM2, MM3, OPLS-UA,
OPLS-AA, OPLS-AA/L and our AMOEBA polarizable atomic multipole-based
potential.Other force fields can be added via new parameter files; ENCAD and
UFF are under consideration presently.

     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) normal mode vibrational analysis,
(4) distance geometry including an efficient random pairwise metrization,
(5) building protein and nucleic acid structures from sequence, (6) simulated
annealing with various cooling protocols, (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) fitting of intermolecular potential
parameters to structural and thermodynamic data, and (13) global optimization
via energy surface smoothing including our own Potential Smoothing and Search
(PSS) method.

     Analytical Cartesian derivatives through the Hessian and analytical
torsional derivatives through the gradient are available. Energy minimization
and vibrational analysis can be performed in either Cartesian or torsional
spaces. 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 types of computations or 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 cutoff using smoothing windows via double loop
searches or the Method of Lights. Particle mesh Ewald (PME) is available for
partial charges, and standard Ewald 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, are implemented. User-
defined potentials can be 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 dialect that makes
use of some common extensions to the Fortran77 standard. Program control is
via an optional Keyword Parameter file. TINKER coordinate input files are also
compatible with Cambridge Scientific Software's CHEMDRAW & CHEM3D programs
and with the gOpenMol, MOLDEN and ReView molecule viewers. A modified version
of RasMol for TINKER is also available for viewing molecular structures.
Auxiliary programs are provided to convert Protein Data Bank files to and
from the TINKER formats. Output can also be generated in formats compatible
with the Tripos Sybyl, Accelrys InsightII, and Xmakemol programs.

Selected References:

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

2.  P. Ren and J. W. Ponder, Consistent Treatment of Inter- and Intramolecular
Polarization in Molecular Mechanics Calculations, J. Comput. Chem., 23,
1497-1506 (2002).

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

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

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

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

Availability:   Executables and Source at http://dasher.wustl.edu/tinker/
Version:        TINKER 4.2 and Force Field Explorer 4.2 of June 2004
Language:       Fortran77 with common extensions and some C,
                Complete C translation via f2c available,
                FFE GUI in Java with Java 3D extensions
Lines of Code:  134,500 in TINKER Package (Fortran77 and some C)
                30,000 in Force Field Explorer (Java and some C)
