Introduction.

Amber is the collective name for a suite of programs that allow users to carry out molecular dynamics simulations, particularly on biomolecules. None of the individual programs carries this name, but the various parts work reasonably well together, and provide a powerful framework for many common calculations. The term amber is also sometimes used to refer to the empirical force field that is implemented here. It should be recognized however, that the code and force field are separate: several other computer packages have implemented the amber force field, and other force fields can be implemented with the amber programs. Further, the force field is in the public domain, whereas the codes are distributed under a license agreement.

Amber 6 (1999) represents a significant change from the most recent previous version, Amber 5, which was released in 1997. Briefly, the major differences include:

1. A major re-write of the particle-mesh-Ewald (PME) implementation for molecular dynamics in sander. This now accurately conserves energy (in the NVE ensemble) over long trajectories, supports alternate box shapes (such as the truncated octahedron), and allows polarizable potentials to be used in conjunction with PME. The user interface for PME calcluations has been greatly simplified, so that in most cases the default parameters should give efficient yet acceptably accurate results. A variety of accuracy checks and comparisons to "regular" Ewald summation results are available.
2. NMR refinements can be carried out with restraints derived from residual dipolar coupling measurements, or with "ambiguous" restraints whose corresponding NMR spectra are not fully assigned, or for "multiple-conformer" models generated using the LES algorithm. Routines to generate restraint input and to interface to NMR data-processing programs have been considerable expanded.
3. Solvent interactions can be approximated with a pairwise generalized Born model that uses continuum solvent ideas to simulate the electrostatic effects of water and of added counterions. An approximate surface area algorithm is also included to provide a simple model for non-polar solvation effects.
4. The trajectory analysis program PTRAJ has been considerably extended, allowing for new analyses, including time correlation functions of interest in NMR and fluorescence anisotropy decay.
5. A script is provided ("MM-PBSA") to automate the energetic analysis of molecular dynamics trajectories using continuum solvent ideas, allowing for estimates of free energies of ligand binding and other conformational changes.
6. The OWFEG ("one window free energy grid") method has been added to assist in ligand/inhibitor design through approximate free energy methods.
7. The roar molecular dynamics module has been extended to include PME and a multiple-time-step integrator.

The following paragraphs outline briefly the changes made between Amber 4.1 (1995) and Amber 5 (1997):

1. an updated and parallelized implementation of the particle-mesh Ewald routine, and its incorporation into the free energy module;
2. "locally-enhanced sampling" (LES) code that allows parts of the system to be present as multiple copies;
3. an alternate version of Sander (ROAR) that includes the ability to define part of the system as a quantum-mechanical section (QM/MM), and includes alternate integrators;
4. PROFEC (Pictorial Representation of Free Energy Changes), a set of tools for carrying out and displaying extrapolative free energy changes;
5. new and parallelized methods for NMR refinement; incorporation of penalites based on pseudocontact shifts.
6. updates to the functionality and stability of LEaP.