Coarse-grained protein models

This work reports our eff ort to develop a coarse-grained protein model that can be used to smdy protein-protein interactions in multi-protein systems via DMD simulations. We deploy a two-bead-per-residue protein model one bead for the backbone and the other for the sidechain. The parameters of our protein model are obtained by coarse-graining atomistic simulation results for backbone-backbone, backbone-sidechain, and sidechain-sidechain interactions in explicit water. The rest of the paper is organized as follows. Section 2 describes the protein model in detail Sect. 3 describes the atomistic and DMD simulations Sect. 4 discusses the analysis leading to the final choice of model parameters and Sect. 5 summarizes the current status of the model. 

Fig. 6.31 Normalised intermediate scattering function from C-phycocyanin (CPC) obtained by spin-echo [335] compared to a full MD simulation (solid line) exhibiting a good quantitative matching. In contrast the MD results from simplified treatments as from protein without solvent (long dash-short dash /me), with point-like residues (Cpt-atoms) (dashed line) or coarse grained harmonic model (dash-dotted line) show similar slopes but deviate in particular in terms of the amplitude of initial decay. The latter deviation are (partly) explained by the employed technique of Fourier transformation. (Reprinted with permission from [348]. Copyright 2002 Elsevier)...

The fastest proteins fold amazingly quickly some as fast as a millionth of a second. While this time is very fast on a person s timescale, it is remarkably long for computers to simulate. In fact, there is about a 1000-fold gap between the simulation timescales and the times at which the fastest proteins fold. This is why the simulation of collapse kinetics is extremely computationally demanding. Thus, the current challenge lies in understanding how particular chemical sequences in coarse-grained copolymer models lead to particular collapse features. This is a fundamental issue in the problem. 

Electrostatic Interactions between RNA and Protein Capsid in Cowpea Chlorotic Mottle Virus Simulated by a Coarse-grain RNA Model and Monte Carlo Approach. 

A step closer toward realism is taken by off-lattice models in which the backbone is specified in some detail, while side chains, if they are represented at all, are taken to be single, unified spheres [44-50]. One indication that this approach is too simplistic was given in [51], which proved that for a backbone representation in which only Ca carbons were modeled, no contact potential could stabilize the native conformation of a single protein against its nonnative ( decoy ) conformations. However, Irback and co-workers were able to fold real protein sequences, albeit short ones, using a detailed backbone representation, with coarse-grained side chains modeled as spheres [49, 52-54]. 

Polymers to Proteins, NIC Symposium Series, Jiilich, Germany, 2004, pp. 83—140. Monte Carlo Simulation of Polymers Coarse-Grained Models. 

Lattanzi, G., and Maritan, A. (2004). Coarse grained models The kinetics of motor proteins. Comput. Mater. Sd. 30, 172-179. 

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