This paper presents an extension of the Gaussian Network Model (GNM) to account for anisotropic fluctuations in proteins, referred to as the Anisotropic Network Model (ANM). The GNM, which has been successfully used to describe the fluctuation dynamics of proteins, assumes isotropic motion of residues around their mean positions. However, anisotropic motion is crucial for understanding protein mechanisms and function. The ANM is derived from the second derivatives of the overall potential and provides a 3D description of the internal modes of motion. The theory is applied to the retinol-binding protein (RBP), a β-barrel protein, to illustrate its utility. The cutoff distance and force constant for inter-residue interactions in the ANM are determined, and the vibrational frequencies are compared with experimental data. The anisotropy of motion is analyzed, revealing regions of enhanced flexibility and suggesting that these regions are important for ligand binding and recognition. The ANM provides a valuable tool for understanding the collective motions and functional mechanisms of proteins.This paper presents an extension of the Gaussian Network Model (GNM) to account for anisotropic fluctuations in proteins, referred to as the Anisotropic Network Model (ANM). The GNM, which has been successfully used to describe the fluctuation dynamics of proteins, assumes isotropic motion of residues around their mean positions. However, anisotropic motion is crucial for understanding protein mechanisms and function. The ANM is derived from the second derivatives of the overall potential and provides a 3D description of the internal modes of motion. The theory is applied to the retinol-binding protein (RBP), a β-barrel protein, to illustrate its utility. The cutoff distance and force constant for inter-residue interactions in the ANM are determined, and the vibrational frequencies are compared with experimental data. The anisotropy of motion is analyzed, revealing regions of enhanced flexibility and suggesting that these regions are important for ligand binding and recognition. The ANM provides a valuable tool for understanding the collective motions and functional mechanisms of proteins.