Coarse-Grained Model of Proteins Incorporating Atomistic Detail of the Active Site

Neri, Marilisa; Anselmi, Claudio; Cascella, M.; Maritan, Amos; Carloni, Paolo

doi:10.1103/physrevlett.95.218102

Cited by 167 publications

(192 citation statements)

References 30 publications

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“…24 Interactions between sites of different resolution in such a multiscale system can be defined with special mixing rules, 25 or through complete reparameterization of all AA-CG cross interactions. 26 In the work of Neri et al, 27 only a protein system is considered with an explicit interface region located between the AA and CG parts in order to bridge the discontinuity between the two models. Further background on the emerging field of multiscale modeling methods can be found in recent reviews.…”

Section: Introductionmentioning

confidence: 99%

Hybrid simulations: combining atomistic and coarse-grained force fields using virtual sites

Rzepiela

Louhivuori

Peter

et al. 2011

Phys. Chem. Chem. Phys.

190

198

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Hybrid simulations, in which part of the system is represented at atomic resolution and the remaining part at a reduced, coarse-grained, level offer a powerful way to combine the accuracy associated with the atomistic force fields to the sampling speed obtained with coarse-grained (CG) potentials. In this work we introduce a straightforward scheme to perform hybrid simulations, making use of virtual sites to couple the two levels of resolution. With the help of these virtual sites interactions between molecules at different levels of resolution, i.e. between CG and atomistic molecules, are treated the same way as the pure CG-CG interactions. To test our method, we combine the Gromos atomistic force field with a number of coarse-grained potentials, obtained through several approaches that are designed to obtain CG potentials based on an existing atomistic model, namely iterative Boltzmann inversion, force matching, and a potential of mean force subtraction procedure (SB). We also explore the use of the MARTINI force field for the CG potential. A simple system, consisting of atomistic butane molecules dissolved in CG butane, is used to study the performance of our hybrid scheme. Based on the potentials of mean force for atomistic butane in CG solvent, and the properties of 1 : 1 mixtures of atomistic and CG butane which should exhibit ideal mixing behavior, we conclude that the MARTINI and SB potentials are particularly suited to be combined with the atomistic force field. The MARTINI potential is subsequently used to perform hybrid simulations of atomistic dialanine peptides in both CG butane and water. Compared to a fully atomistic description of the system, the hybrid description gives similar results provided that the dielectric screening of water is accounted for. Within the field of biomolecules, our method appears ideally suited to study e.g. protein-ligand binding, where the active site and ligand are modeled in atomistic detail and the rest of the protein, together with the solvent, is coarse-grained.

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Section: Introductionmentioning

confidence: 99%

Hybrid simulations: combining atomistic and coarse-grained force fields using virtual sites

Rzepiela

Louhivuori

Peter

et al. 2011

Phys. Chem. Chem. Phys.

190

198

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“…None of these techniques has been used to simulate transmembrane permeation processes. In fact, applications to biological systems have been so far limited to the modeling of basic structural and dynamical properties of proteins, 18,19 and to the study of the structure of a preassembled membrane-protein system. 20 In these approaches, problems arise whenever molecules diffuse across regions of different representations, as the models for the AL and CG particles are not compatible.…”

Section: Introductionmentioning

confidence: 99%

“…Several multiresolution approaches have been reported in the literature. [17][18][19][20][21][22][23][24] While these methods are generally promising, a number of issues can be noted. Most of the multiresolution schemes developed so far are characterized by the use of rather complex algorithms to specifically model the interfacial region between the AL and CG parts of the system.…”

Section: Introductionmentioning

confidence: 99%

Permeability of Small Molecules through a Lipid Bilayer: A Multiscale Simulation Study

2009

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The transmembrane permeation of eight small (molecular weight <100) organic molecules across a phospholipid bilayer is investigated by multiscale molecular dynamics simulation. The bilayer and hydrating water are represented by simplified, efficient coarse-grain models, whereas the permeating molecules are described by a standard atomic-level force-field. Permeability properties are obtained through a refined version of the z-constraint algorithm. By constraining each permeant at selected depths inside the bilayer, we have sampled free energy differences and diffusion coefficients across the membrane. These data have been combined, according to the inhomogeneous solubility-diffusion model, to yield the permeability coefficients. The results are generally consistent with previous atomic-level calculations and available experimental data. Computationally, our multiscale approach proves 2 orders of magnitude faster than traditional atomic-level methods.

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“…Their efficiency and scope increases significantly if two or more such different approaches are combined into hybrid multiscale schemes. This is the case for the quantum based QM/MM ap-proach [4] and that of dual scale resolution techniques [5,6,7,8,9,10,11,12,13,14,15,16,17,18] aiming at bridging the atomistic and mesoscale length scale. However, the common feature and limitation of all these methods is the fact that the regions or parts of the system treated at different level of resolution are fixed and do not allow for free exchange.…”

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confidence: 99%

Adaptive molecular resolution via a continuous change of the phase space dimensionality

2007

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For the study of complex synthetic and biological molecular systems by computer simulations one is still restricted to simple model systems or to by far too small time scales. To overcome this problem multiscale techniques are being developed for many applications. However in almost all cases, the regions of different resolution are fixed and not in a true equilibrium with each other. We here give the theoretical framework for an efficient and flexible coupling of the different regimes. The approach leads to an analog of a geometry induced phase transition and a counterpart of the equipartition theorem for fractional degrees of freedom. This provides a rather general formal basis for advanced computer simulation methods applying different levels of resolution. A long standing and often most challenging problem in condensed matter physics, up to some simple crystalline materials, is to understand the microscopic origin of macroscopic properties. While in certain cases a microscopic scale can be clearly separated from a macroscopic one, this is not the case for most experimental systems -details of the local interaction and generic/universal aspects are closely related. Already the proper determination of the fracture energy and crack propagation in crystalline materials requires a hierarchical and interrelated description, which links the breaking of the interatomic bonding in the fracture region to the response of the rest of the system on a micron scale [1]. The presence of microscopic chemical impurities in many metals and alloys changes their macroscopic mechanical behavior [2,3]. Even more complicated are synthetic and biological soft matter systems. Whether one is dealing with the morphology, the glass transition of a polymeric system, the function of a molecular assembly, e.g. for electronic applications or studies ligand-protein recognition or protein-protein interaction, in all cases the generic soft matter properties, such as matrix or chain conformation fluctuations, and details of the local chemistry apply to roughly the same length scales. For all these problems, which due to their complexity are heavily studied by computer simulations, there is a common underlying physical scenario: the number of degrees of freedom (DOFs) involved is very large and the exhaustive exploration of the related phase space is prohibitive. For many questions, however, such a deep level of detail in the description is only required locally.Theoretical methods employed to study these systems span from quantum-mechanical to macroscopic statistical approaches. Their efficiency and scope increases significantly if two or more such different approaches are combined into hybrid multiscale schemes. This is the case for the quantum based QM/MM ap- * On leave from the National

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Coarse-Grained Model of Proteins Incorporating Atomistic Detail of the Active Site

Cited by 167 publications

References 30 publications

Hybrid simulations: combining atomistic and coarse-grained force fields using virtual sites

Hybrid simulations: combining atomistic and coarse-grained force fields using virtual sites

Permeability of Small Molecules through a Lipid Bilayer: A Multiscale Simulation Study

Adaptive molecular resolution via a continuous change of the phase space dimensionality

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