Table 1.

Strong and Weak Points of the Amber Biomolecular Simulation Programs.

Strengths	Weaknesses
Amber implements efficient simulations with periodic boundary conditions, using the PME method for electrostatic interactions and a continuum model for long-range van der Waals interactions.	One cannot do good simulations of just part of a system, such as the active site of an enzyme: stochastic boundary conditions for the water-continuum interface are missing, as are efficient means for handling long-range electrostatics and a reaction field.
Non-periodic simulations are supported, using a generalized Born or numerical Poisson-Boltzmann implicit solvent model.	The component programs lack a consistent user interface; there is only limited scripting capability to support types of calculations not anticipated by the authors.
Explicit support is provided for carbohydrate simulations, as well as for proteins, nucleic acids and small organic molecules.	There is limited support for force fields other than those developed by Amber contributors.
Free-energy calculations use thermodynamic integration or umbrella sampling techniques, and are not limited to pairwise decomposable potentials.	Missing features include: “dual topology” free energy calculations, reaction-path analysis, Monte Carlo sampling, torsion angle dynamics, and interactive steered molecular dynamics.
Convergence acceleration can use locally-enhanced sampling or replica exchange techniques.	QM/MM simulations are limited to semiempirical Hamiltonians, and cannot currently be combined with the PME or generalized Born solvation options.
There is a extensive support for trajectory analysis and energetic post-processing.	The codes were written by many authors over many years, and much of it is difficult to understand or modify.
Restraints can be very flexible, and can be based on many types of NMR data.	Efficient parallel scaling beyond about a dozen processors may required access to special hardware or the adoption of an implicit solvent model.
There is a large and active user community, plus tutorials and a User’s Manual to guide new users. The source code is portable and is available for inspection and modification.	Users are required to compile the programs themselves, and it can be tedious to assemble the needed compilers and libraries.