Protein structure and dynamics and, therefore, their biological functions are dictatedxs by a collection of forces that vary from those associated with covalent linkages, such as bonds, to long-range through space forces, such as electrostatic or coulombic interactions. Accordingly, to be able to apply theoretical approaches to understand the behavior of proteins, it is necessary to be able to accurately predict the change in energy of a protein as a function of the change in conformation. Importantly, such predictions must include contributions from the environment in which the protein is immersed. While quantum-mechanical (QM) methods are attractive in their ability to model complex chemical phenomena at the level of electronic structure, such methods are typically inappropriate for proteins due to the large size of these macromolecules as well as the need to treat their environment in an explicit fashion. Rather, molecular mechanics (MM), which rely on potential energy functions or empirical force fields, afford the computational speed to allow for calculations on proteins along with their environment.


Potential Energy Function Valence Angle Partial Atomic Charge Hydration Free Energy Generalize Born 
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  • Alexander D. MacKerellJr.

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