The GLYCAM06 force field is a generalizable biomolecular force field that is no longer specific to carbohydrates and is not dependent on the AMBER force field. It includes all relevant force field terms and uses explicit parameters without default or generic values. The new GLYCAM is extendable to all molecular classes, similar to small-molecule force fields. Torsion terms were derived from quantum mechanical data for minimal molecular fragments and small molecules. For carbohydrates, a single parameter set applies to both α- and β-anomers and all monosaccharide ring sizes and conformations. The approach of deriving dihedral parameters by fitting to quantum mechanical data for internal rotational energy curves leads to correct rotamer populations in molecular dynamics simulations and removes the need for phase corrections in dihedral terms. However, there are cases where this approach is inadequate. The new force field is shown to reproduce gas-phase properties of small molecules and rotamer populations for key small molecules and biopolymer building blocks in explicit water, as well as crystalline lattice properties. The GLYCAM06 force field was developed to be transferable to all carbohydrate ring conformations and sizes, self-contained, and applicable to monosaccharides and complex oligosaccharides. It avoids the use of 1–4 electrostatic or non-bonded scaling factors. The parameterization of GLYCAM06 used training and test sets of ~100 molecules from various chemical families. Quantum mechanical calculations were performed using Gaussian98, and molecular mechanics calculations were performed using AMBER754 or AMBER855. Molecular dynamics simulations were carried out with explicit solvent (TIP3P) under isothermal–isobaric conditions. The potential of mean force calculations were performed using the weighted histogram analysis method. Single molecule and ensemble-averaged charge calculations were performed using the restrained electrostatic potential (RESP) charge fitting methodology. The GLYCAM06 force field was validated against experimental data for various molecules, including hydrocarbons, alcohols, ethers, amides, esters, carboxylates, and simple ring systems. The force field was shown to accurately reproduce the gas-phase relative energies of hydrocarbons, the rotational barriers of alcohols, and the conformational properties of carbohydrates. The GLYCAM06 force field was also shown to accurately reproduce the vibrational frequencies of α-D-glucopyranose and the conformational preferences of diols. The force field was validated against experimental data for various molecules, including hydrocarbons, alcohols, ethers, amides, esters, carboxylates, and simple ring systems. The GLYCAM06 force field was shown to accurately reproduce the gas-phase relative energies of hydrocarbons, the rotational barriers of alcohols, and the conformational properties of carbohydrates. The force field was also shown to accurately reproduce the vibrationalThe GLYCAM06 force field is a generalizable biomolecular force field that is no longer specific to carbohydrates and is not dependent on the AMBER force field. It includes all relevant force field terms and uses explicit parameters without default or generic values. The new GLYCAM is extendable to all molecular classes, similar to small-molecule force fields. Torsion terms were derived from quantum mechanical data for minimal molecular fragments and small molecules. For carbohydrates, a single parameter set applies to both α- and β-anomers and all monosaccharide ring sizes and conformations. The approach of deriving dihedral parameters by fitting to quantum mechanical data for internal rotational energy curves leads to correct rotamer populations in molecular dynamics simulations and removes the need for phase corrections in dihedral terms. However, there are cases where this approach is inadequate. The new force field is shown to reproduce gas-phase properties of small molecules and rotamer populations for key small molecules and biopolymer building blocks in explicit water, as well as crystalline lattice properties. The GLYCAM06 force field was developed to be transferable to all carbohydrate ring conformations and sizes, self-contained, and applicable to monosaccharides and complex oligosaccharides. It avoids the use of 1–4 electrostatic or non-bonded scaling factors. The parameterization of GLYCAM06 used training and test sets of ~100 molecules from various chemical families. Quantum mechanical calculations were performed using Gaussian98, and molecular mechanics calculations were performed using AMBER754 or AMBER855. Molecular dynamics simulations were carried out with explicit solvent (TIP3P) under isothermal–isobaric conditions. The potential of mean force calculations were performed using the weighted histogram analysis method. Single molecule and ensemble-averaged charge calculations were performed using the restrained electrostatic potential (RESP) charge fitting methodology. The GLYCAM06 force field was validated against experimental data for various molecules, including hydrocarbons, alcohols, ethers, amides, esters, carboxylates, and simple ring systems. The force field was shown to accurately reproduce the gas-phase relative energies of hydrocarbons, the rotational barriers of alcohols, and the conformational properties of carbohydrates. The GLYCAM06 force field was also shown to accurately reproduce the vibrational frequencies of α-D-glucopyranose and the conformational preferences of diols. The force field was validated against experimental data for various molecules, including hydrocarbons, alcohols, ethers, amides, esters, carboxylates, and simple ring systems. The GLYCAM06 force field was shown to accurately reproduce the gas-phase relative energies of hydrocarbons, the rotational barriers of alcohols, and the conformational properties of carbohydrates. The force field was also shown to accurately reproduce the vibrational