CHARMM empirical energy function

Force-field-based scoring functions use arbitrary empirical estimates of interaction energies obtained by molecular mechanics energy functions. This simple approximation, which takes into account only enthalpic contribution often correlates well with the experiment. Solvent effects are described by atom-based solvation parameters, which are computed for the surface of both ligand and receptor which is buried upon complexation. DOCK-chemical27 and CHARMm scoring functions represent this class. 

King et al. (292)used an empirical binding Ifee-energy function when docking MVT-101 to HIV protease. Forty-nine translation/rota-tions were examined with the Ponder/Richard rotamer library. Only a limited number of retainers for each amino acid were examined Thr(2), Ile(3), Nle(3), Nle(3), Gln(6), and Arg(5). According to the authors, 2.24 x 10 ° discrete states were examined. Sixty-four low ener structures with an average rmsd of 1.36 A were found. If the CHARMM potential was used with the same protocol, then the av-eragQ rmsd was increased to 1.68 A. 

The CHARMM code, version c25bl, was chosen for integration with the metal potential. CHARMM is a multi-purpose molecular dynamics program [35], which uses empirical potential energy functions to simulate a variety of systems, including proteins, nucleic acids, lipids, sugars and water. The availability of periodic boundary conditions of various lattice types (for example cubic and orthorhombic) makes it possible to treat solids as well as liquids. 

The success of any molecular simulation method relies on the potential energy function for the system of interest, also known as force fields [27]. In case of proteins, several (semi)empirical atomistic force fields have been developed over the years, of which ENCAD [28,29], AMBER [30], CHARMM [31], GRO-MOS [32], and OPLSAA [33] are the most well known. In principle, the force field should include the electronic structure, but for most except the smallest systems the calculation of the electronic structure is prohibitively expensive, even when using approximations such as density functional theory. Instead, most potential energy functions are (semi)empirical classical approximations of the Born-Oppenheimer energy surface. 

In this work, a recently developed semi-empirical method, SCC-DFTB method, is employed to account for the electronic structure of QM part. The details of this method and its implementation to CHARMM have been summarized elsewhere [6, 22-24]. Here we just give a short description. This method is derived by a second order expansion of the DFT total energy functional with respect to the charge density fluctuation around a given reference density. The total energy can be expressed as following [22] ... 

Molecular modeling and computer simulation with empirical potential energy function (force field) are now routinely carried out to help understand and predict structures and dynamics of proteins and other macromolecules of biological relevance in water and membrane environments. After over 40 years of development, popular force fields such as AMBER, CHARMM, OPLS and GROMOS have been widely employed in biomolecular simulations. These force fields are used dominantly in highly optimized molecular dynamics... 

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