CHARMM force-fields/model

We conclude this section by giving a topical example of the utility of conditional averages in considering molecularly complex systems (Ashbaugh et al, 2004). We considered the RPLC system discussed above (p. 5), but without methanol n-Ci8 alkyl chains, tethered to a planar support, with water as the mobile phase. The backside of the liquid water phase contacts a dilute water vapor truncated by a repulsive wall see Fig. 1.2, p. 7. Thus, it is appropriate to characterize the system as consistent with aqueous liquid-vapor coexistence at low pressure. A standard CHARMM force-field model (MacKerell Jr. et al, 1998) is used, as are standard molecular dynamics procedures - including periodic boimdary conditions - to acquire the data considered here. Our interest is in the interface between the stationary alkyl and the mobile liquid water phases at 300 K. 

In an attempt to aid interpretation of the IR spectrum of MbCO we decided to model the full protein by use of a hybrid quantum mechanics/molecular mechanics approach (QM/MM), to evaluate changes in the CO stretching frequency for different protein conformations. The QM/MM method used [44] combines a first-principles description of the active center with a force-field treatment (using the CHARMM force field) of the rest of the protein. The QM-MM boundary is modeled by use of link atoms (four in the heme vinyl and propionate substituents and one on the His64 residue). Our QM region will include the CO ligand, the porphyrin, and the axial imidazole (Fig. 3.13). The vinyl and propionate porphyrin substituents were not included, because we had previously found they did not affect the properties of the Fe-ligand bonds (Section 3.3.1). It was, on the other hand, crucial to include the imidazole of the proximal His (directly bonded to the... 

Hypercube, Inc. at http //www.hyper.com offers molecular modeling packages under the HyperChem name. HyperChem s newest version, Hyper-Chem Release 7.5, is a full 32-bit application, developed for the Windows 95, 98, NT, ME, 2000, and XP operating systems. Density Functional Theory (DFT) has been added as a basic computational engine to complement Molecular Mechanics, Semiempirical Quantum Mechanics and ab initio Quantum Mechanics. The DFT engine includes four combination or hybrid functions, such as the popular B3-LYP or Becke-97 methods. The Bio+ force field in HyperChem represents a version of the Chemistry at HARvard using Molecular Mechanics (CHARMM) force field. Release 7.5 of HyperChem updates... 

For the construction of molecular structures, a 2D formula editor is provided in combination with 3D conversion. Standard potential energy minimization is performed using the modified parameter set of the CHARMm force field [68] the conformational models are built using Monte Carlo conformational analysis together with poling as described in the next section. 

In simulations involving explicit water, it is crucial that a balance exists between water-protein and water-water interactions in order to describe correctly the water-protein interface. This of course depends on the choice of water model to be used with the protein force-field. The developers of most modern force-fields for protein simulations have chosen a specific water model which has then used as the foundation of the force-field parameterisation. In the following we consider the parameter sat ion of the Charmm force-field, although other force-fields have used similar approaches. 

Alanine dipeptide, see Fig. 10.30, is a useful model compound in that it contains the basic constituents of a peptide chain. Thus there are sp -sp backbone C-C bond, backbone N-C bonds and side-chain C-C bonds. The torsions about each of these bonds are denoted as F, O and % respectively. The compound in the solid state has been modelled by molecular mechanics using the CHARMM force field [76]. The best results required non-zero force constants for the T and O torsions. Fig. 10.31 compares the experimental spectrum with the calculated one. There is a uniform mismatch in frequencies of 35 cm", but the overall pattern is reproduced. The individual contributions of the methyl groups... 

As an example of the relative performance of explicit and implicit solvation models in calculations of conformational equilibria, Scarsi et al. [60] compared the calculated conformational properties obtained by the CHARMM force field of liquid 1,2-dichloroethane and of terminally blocked alanine dipeptide in aqueous solution. They employed (i) a systematic conformational search with solvation energies cal-... 

For each of these interactions, a model complex was designed the BSSE-corrected MP2 interaction potential energy surface (IPES) was calculated then the CHARMm IPES was validated against the MP2 one. If the CHARMm force field cannot produce a satisfactory IPES, the force field will be reparameterized using an automatic least square optimization program OPTMM written by G.D. in C language [24]. 

BjeUcmar, P., P. Larsson, M. A. Cuendet, B. Hess, and E. Lindahl. 2010. Implementation of the CHARMM force field in GROM ACS Analysis of protein stability effects from correction maps, virtual interaction sites, and water models. Journal of Chemical Theory and Computation. 6, 459. 

Water shells of fibrillar and globular proteins ate studied. The simulations ate held in T1P3P water potential using CHARMM force field. The water shell topology and internal parameters have been analyzed in terms of statistical characteristics and specific examples of water structures. Some of the structures obtained correspond to the Bulienkov parametrical model of bonded water. 

FIGURE 3.2 (a) HRTEM image of AC (5 bet= 1664 m /g) showing the turbostratic structure and (b) an AC model with the geometry optimized by MM (CharMM force field) and then by semiempirical method PM6. (A Taken from Carbon, 50, Gun ko, V.M., Kozynchenko, O.P., Tennison, S.R., Leboda, R., Skubiszewska-Zi ba, J., and Mikhalovsky, S.V., Comparative study of nanopores in activated carbons by HRTEM and adsorption methods, 3146-3153, 2012a. Copyright 2012, with permission from Elsevier.)... 

It is interesting to compare the possibilities and errors of different hybrid QM/MM schemes. The careful examination and comparison of link atom and LSCF techniques was performed in Ref. [128] using the CHARMM force field [114] and the AMI method [143] as a quantum chemical procedure. In the case of the link atom procedure two options were used QQ - the link atom does not interact with the MM subsystem and HQ - link atom interacts with all MM atoms. The main conclusion of this consideration is that the LSCF and the link atom schemes are of similar quality. The error in the proton affinity determination induced by these schemes is several kcal/mol. It is noteworthy that all the schemes work rather badly in description of conformational properties of n-butane. The large charge on the MM atoms in the proximity of the QM subsystem (especially on the boundary atom) cause significant errors in the proton affinity estimates for all methods (especially, in the case of the LSCF approach where the error can be of tens of kcal/mol). This is not surprising since the stability and transferability of intrabond one- and two-electron density matrix elements Eq. (19) is broken here. It proves that the simple electrostatic model is not well appropriate for these schemes and that a detailed analysis of the... 

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