        TINKER ­ Software Tools for Molecular Design

      Jay Ponder Lab, Dept. of Biochemistry & Molecular 
                         Biophysics,
    Washington University School of Medicine, St. Louis, 
                       Missouri 63110

     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-95, CHARMM22, MM2(1991), MM3(2000), 
OPLS-AA,  OPLS-UA  and  our TINKER  potential.  Other  force 
fields can be added via new parameter files; ENCAD, MMFF and 
UFF are under consideration for future addition.

     Programs  are   provided  to  perform   many  functions 
including  the  following:   (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)  a  simple  free  energy  perturbation  facility,  (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.

     The  TINKER package  is written  in a  portable Fortran 
dialect  that makes  use of  some common  extensions to  the 
Fortran-77  standard. Program  control  is  via an  optional 
Keyword  Parameter file.  A modified  version of  RasMol for 
TINKER  is available  for  viewing  molecular structures.  A 
complete GUI  in Java is currently  under active development 
and  planned for  future  release.  TINKER coordinate  input 
files   are  also   compatible  with   Cambridge  Scientific 
Software's CHEMDRAW & CHEM3D programs and with the gOpenMol, 
MOLDEN and  ReView molecule viewers. Auxiliary  programs are 
provided to  convert Brookhaven  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. 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).
2. 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).
3. M. J. Dudek  and J. W.  Ponder, Accurate Modeling  of the 
   Intramolecular  Electrostatic  Energy  of   Proteins,  J. 
   Comput. Chem., 16, 791-816 (1995).
4. Y. Kong and J. W. Ponder, Reaction Field Methods for Off-
   Center Multipoles, J. Chem. Phys., 107, 481-492 (1997).
5. M.  Dudek,  K.  Ramnarayan  and  J.  W.  Ponder,  Protein 
   Structure Prediction  Using  a  Combination  of  Sequence 
   Homology  and  Global  Energy   Minimization  II.  Energy 
   Functions, J. Comput. Chem., 19, 548-573 (1998).
6. 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).

Availability:       http://dasher.wustl.edu/tinker/
Version:       TINKER 3.9 of June 2001
Language:           Fortran-77 with common extensions,
               C translation via f2c available,
               Fortran-90 version under development
Lines of Code:      Approximately 118,000 including comments
