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.

The best overview of AMBER is in the following paper: D.A. Pearlman, D.A. Case, J.W. Caldwell, W.R. Ross, T.E. Cheatham, III, S. DeBolt, D. Ferguson, G. Seibel and P. Kollman. AMBER, a computer program for applying molecular mechanics, normal mode analysis, molecular dynamics and free energy calculations to elucidate the structures and energies of molecules. Computer Physics Communications 91, 1-41 (1995).

The most recent version of AMBER is version 6.0, released in January, 2000. Principal revisions from earlier versions include:

  • LES with PME. AMBER 5 contained the capability for Locally Enhanced Sampling (LES) and Particle Mesh Ewald (PME), but not both together. These have been integrated and used in promising ways in prediction of RNA structure (Simmerling et al, JACS, 120:7149, 1998) and protein structure (Simmerling et al, JACS,submitted) as well as in free energy calculations of carbohydrate systems (Simmerling et al, JACS, 120:5771, 1998, and work in progress). We anticipate this methodology will be very powerful in structure prediction of complex molecules in solution, since, in contrast to most other methods, explict water molecules can be included and thus the solvation effect considered at the highest level of accuracy.

  • CMC/MD Chemical Monte Carlo/Molecular Dynamics(CMC/MD) is a new approach to ligand design, which can consider many molecules at once and is a powerful complement to more qualitative approaches. In papers published by Pitera and Kollman (JACS, 120:7557, 1998) and by Eriksson et al. (J. Med. Chem., 42:868, 1999), it has been shown to be accurate and leads in both cases to a ligand which was predicted to bind more strongly to the target than the previous best one considered experimentally.

  • Generalized PROFEC Radmer and Kollman (J Comput-Aided Mol Des, 12:215, 1998) have shown that a method called PROFEC(pictorial representation of free energy components) can give useful ideas on drug design, based on running simulations of ligands free and bound to a target protein or nucleic acid. Pearlman has recently expanded and improved this method to increase its generality and power (Pearlman, submitted for publication).

  • MM-PBSA (Molecular Mechanics-Poisson Bolzmann/Surface Area) Case et al. (JACS 120:9401, 1998) have shown that a combination of molecular dynamics simulations and continuum calculations can be very powerful in estimating free energy differences even between systems on which one cannot use free energy perturbation calculations. This methodology is automated in AMBER 6. This method has proven to be very powerful in calculations of protein-ligand interactions (Chong et al, PNAS, in press), in protein-peptide interactions (Massova and Kollman, JACS, 121:8133, 1999), RNA-protein interactions (Reyes and Kollman, JMB, in press) and protein folding (Lee et al, Proteins, submitted.)

  • GB/SA Generalized Born surface area(GB/SA) is a way to put solvation effects implicitly into calculations of complex systems and recently Tsui and Case have incorporated this into AMBER 6 for use in minimization and molecular dynamics calculations.

  • Revised PME implementation AMBER 6 contains 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.

  • 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 considerably expanded.

  • In addition to the capabilities in AMBER 6, a major effort is going on to broaden the applicability of the force field to more functional groups of organic molecules, such that one has an accurate representation of both the conformational and non-bonded interactions of any organic molecule. A paper in this area has been submitted to J. Comp. Chem. (Junmei Wang and PAK, submitted) and Wang is further developing the interface program ANTECHAMBER to enable efficient handling of many molecules at a time.

    The most complete and up-to-date information (including instructions on obtaining AMBER) is maintained at the University of California, San Francisco: 

  • http://www.amber.ucsf.edu/amber/amber.html