Computer programs CHARMM

In this paper we develop a new method for finding the three-dimensional space that surrounds a substrate/ligand. This space, which is the chemical equivalent of the receptor, is represented as a protein structure, referred herein as a "pseudo-receptor". A variety of computational tools are used to create the pseudo-receptor. A molecular mechanics and dynamics program, CHARMm(l), is used to calculate the energy and conformational features of the pseudo-receptor. The program QUANTA(l) is used to define the preliminary protein sequence, secondary structure, graphically examine molecular interactions, interface with CHARMm, and model amino-acid mutations in the protein sequence. 

Nicklaus MC. Conformational energies calculated by the molecular mechanics program CHARMm. J Comput Chem 1997 18 1056-1060. 

One should distinguish between a force field, which is defined by the expression for V in (16.94), and a molecular-mechanics program, which is a computer program that uses a force field to perform molecular-mechanics calculations. Sometimes MM programs and force fields have the same name. For example, CHARMM is also the name of a molecular-mechanics program. The CHARMM program has available in it, not only the CHARMM force field, but also MMFF94. 

The multipole expansion of Coulomb s law up to the octupole, which can be found in [48], is more complicated than Eq. 9.3. The advantage is that the complexity in the expression leads to computational efficiency in computer simulations once it is programmed, since only one distance between two interacting water molecules is needed. The downside is that while it becomes more accurate as higher order multipoles are added, it also becomes computationally slower as higher-order multipoles are included since each n-pole involves a (n - 1) rank tensor. A soft-sphere model with a dipole, quadrupole, and octupole (SSDQO], which is exact up to the 1/r term and in addition approximates the 1/r term, has been developed for computational efficiency [48]. However, the recent implementation of a fast multipole method in the molecular dynamics program CHARMM [80] should make this approximation unnecessary specifically, the full multipole expansion up to the... 

These issues are discussed by Comba and Hambley who also provide a detailed account of how to derive FF parameters as do Norrby and Brandt. Computer programs which have been applied to modeling various coordination compounds include versions of MM2 and MM3, SHAPES,and modified versions of MacroModel, CHARMM, AMBER,MOMEC, ... 

Two well-established computer programs for MD simulations are CHARMM [24] and AMBER [219], which implement a similar functional form of the atomistic force field and include a large number of tools for setting up the files required to run an MD simuIatiOTi. 

Table 3 lists chemists who have been most cited in chapters of prior volumes of our book series. Not surprisingly, all those listed are computational chemists, and many have written a chapter for Reviews in Computational Chemistry. It is interesting to notice how frequently the listed individuals are associated with developing a computer program that is well known in the lexicon of computational chemistry AMBER, CHARMM, Gaussian, UHBD, GROMOS, MM2/MM3, ECEPP, BOSS, DGEOM, MOPAC, DOCK, and so forth. 

MacKerell and coworkers presented a polarizable force field, called Drude-2013, based on the classical Drude oscillator framework, currently implemented in simulation programs CHARMM and NAMD, for modeling of peptides and proteins. It can be used for several hundreds of ns simulations without requiring too much computing power. In its first generation version it gives improved order parameters for certain residues, for which they were underestimated using additive force fields, but does not perform so well yet for NMR chemical shifts. 

Brooks, B.R. Bruccoleri, R.E. Olafson, B.D. States, D.J. Swaminathan, S. Karpins, M. CHARMM A program for macromolecular energy, minimization, and dynamics calculations J. Comput. Chem. 4 187-217, 1983. 

It should also be noted that a force field for a wide variety of small molecules, CHARMm (note the small m, indicating the commercial version of the program and parameters), is available [39] and has been applied to protein simulations with limited success. Efforts are currently under way to extend the CHARMm small molecule force field to make the nonbonded parameters consistent with those of the CHARMM force fields, thereby allowing for a variety of small molecules to be included in computational smdies of biological systems. 

AD MacKerell Jr, B Brooks, CL Brooks III, L Nilsson, B Roux, Y Won, M Karplus. CHARMM The energy function and its paramerization with an overview of the program. In PvR Schleyer, NL Alhnger, T Clark, J Gasteiger, PA Kollman, HP Schaefer III, PR Schreiner, eds. Encyclopedia of Computational Chemistry, Vol 1. Chichester, UK Wiley, 1998, pp 271-277. 

Brooks R, Bruccoleri RE, Olafson BD, States DJ, Swaminathan S, Karplus M (1983) Charmm A program for macromolecular energy minimization and dynamics calculations. J Comput Chem 4 187-217. 

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