Models ECEPP

Some of the more approximate or specialized FFs encountered in the literature include CFF, CHEM-X, COSMIC, CYFF, DREIDING, MMX, SHAPES, TRIPOS, VALBOND, and UFF. Well-known FFs for modeling proteins and nucleic acids include AMBER, CHARMM, ECEPP, GROMOS, OPLS and their variants. Some of these latter FFs compromise the quality of reproducing subtle intramolecular electronic effects for the sake of being fast enough to treat biomacromolecules in long molecular simulations. 

Figure 10 Number of publications per year in the CJACS file mentioning CHARMM, AMBER, GROMOS, ECEPP, or OPLS. The academic version of CHARMM has the last M in uppercase, whereas the spelling CHARMm is used by MSI. Database searching is not case sensitive hence the developer s name was used as part of some of the queries. The search queries for each curve were (1) charmm and (simulation or modeling) and karplus, (2) amber and (simulation or modeling) and kollman (3) biomos or gromos, (4) ecepp, and (5) opls.

Many technical limitations remain to be overcome before ligand design becomes reliable and routine. Many deficiencies in molecular mechanics previously cited remain that limit reliability. Adequate modeling of electrostatics remains elusive in many experimental systems of interest such as membranes. Newer derivations of force fields, such as MM3 (27, 296 and references therein), CHARMM (297, 298), AMBER/OPLS (157), ECEPP (299), and others (156, 300), are attempting to more accurately represent the experimental data, whereas others include a broader spec-... 

Fig. 6. Low-energy structure of the 36-residue chicken villin headpiece sub-domain HP-36. On the left the structure determined in NMR experiments is shown. The right panel shows the lowest-energy configuration found in a feedback-optimized allatom parallel tempering simulation using the ECEPP/2 force field and an implicit solvent model. The root-mean square deviation of this structure to the structure on the left is Rrmsd = 3.8 A...

Applying an all-atom parallel tempering simulation of the protein HP-36 in the ECEPP/2 force field [33] using an implicit solvent model [34] the authors of [27] have measured the diffusion of labeled replicas in temperature space. The simulated temperature interval is chosen such that at the lowest temperature = 250 K the protein is in a folded state and the highest temperature T ax = 1000 K ensures that the protein can fully unfold for the simulated force field. The measured local diffusivity for the random walk between these two extremal temperatures is shown in Fig. 7. A very strong modulation of the local diffusivity is found along the temperature. Note the logarithmic scale of the ordinate. The pronounced minimum of the local diffusivity around T 500 K points to a severe bottleneck in the simulation which by measurements of the specific heat has been identified as the helix-coil... 

Figure 5. Most probable conformation of poly[Ala -1-napAla] predicted from the ECEPP energy calculation. NAMOD version 3) program (ref. 16) was used to draw the molecular models.

Let us consider Met-enkephalin (Tyr-Gly-Gly-Phe-Met) with 75 atomic sites in three different solvents including water. The model of a wee ter molecule is the extended simple point charge (SPG/E) model [19]. It is assumed that the peptide is immersed in the solvent at infinite dilution. The potential-energy functions and parameters are adopted from KONF90 [20] that is based on ECEPP/2 [21]. The peptide and solvent molecules comprise the interaction sites (atoms). The interaction between the peptide molecule and a water molecule is expressed as the sum of the site-site pair interactions that have the form... 

For a significant portion of this work, the ECEPP/3 (Empirical Conformational Energy Program for Peptides) [38] potential model is utilized. In this force field, it is assumed that the covalent bond lengths and bond angles are fixed at their equilibrium values. Then, the conformation is only a function of... 

The JRF ASP set was derived from NMR studies of low energy solvated configurations of 13 tetrapeptides [67]. This represents an important difference from other derivations because actual peptides, rather than simple model compounds, were used to develop the JRF parameters. An ensemble of low-energy stractures for these tetrapeptides was also produced using the ECEPP/2... 

A detailed modeling approach is proposed by using the ECEPP/3 force held [38]. When considering an unconstrained minimization, this approach provides the following objective function ... 

The algorithmic steps for the constrained aBB approach can be generalized to any force field model or routine for solving constrained optimization problems. Here, the otBB approach is interfaced with PACK [74] and NPSOL [28]. PACK is used to transform to and from Cartesian and internal coordinate systems, as well as to obtain function and gradient contributions for the ECEPP/3 force field and the distance constraint equations. NPSOL is a local nonlinear optimization solver that is used to locally solve the constrained upper and lower bounding problems in each subdomain. 

The ECEPP-05 force field (Arnautova et al. 2006 and references therein) is adjusted to both new experimental data and quantum mechanical results. Like previous ECEPP force fields ECEPP-05 utilizes the fixed bond lengths and bond angles but has some distinctive features as compared to both ECEPP/3 version and many other popular force fields. The van der Waals term of the energy is modeled by using the 6-exp potential function... 

As this approach results in very strong steric repulsions it has been termed a hard sphere model. Although the HSEA force field is similar in its use of rigid-residue geometries to early force fields for proteins, such as ECEPP, it has several features that are unique. 

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