S. Yefimov

Bio: S. Yefimov is an academic researcher from University of Groningen. The author has contributed to research in topics: Dislocation & Bauschinger effect. The author has an hindex of 5, co-authored 6 publications receiving 4398 citations.

The MARTINI force field : Coarse grained model for biomolecular simulations

Abstract: We present an improved and extended version of our coarse grained lipid model. The new version, coined the MARTINI force field, is parametrized in a systematic way, based on the reproduction of partitioning free energies between polar and apolar phases of a large number of chemical compounds. To reproduce the free energies of these chemical building blocks, the number of possible interaction levels of the coarse-grained sites has increased compared to those of the previous model. Application of the new model to lipid bilayers shows an improved behavior in terms of the stress profile across the bilayer and the tendency to form pores. An extension of the force field now also allows the simulation of planar (ring) compounds, including sterols. Application to a bilayer/cholesterol system at various concentrations shows the typical cholesterol condensation effect similar to that observed in all atom representations.

A comparison of a statistical-mechanics based plasticity model with discrete dislocation plasticity calculations

Abstract: A two-dimensional nonlocal version of continuum crystal plasticity theory is proposed, which is based on a statistical-mechanics description of the collective behavior of dislocations coupled to standard small-strain crystal continuum kinematics for single slip. It involves a set of transport equations for the total dislocation density field and for the net-Burgers vector density field, which include a slip system back stress associated to the gradient of the net-Burgers vector density. The theory is applied to the problem of shearing of a two-dimensional composite material with elastic reinforcements in a crystalline matrix. The results are compared to those of discrete dislocation simulations of the same problem. The continuum theory is shown to be able to pick up the distinct dependence on the size of the reinforcing particles for one of the morphologies being studied. Also, its predictions are consistent with the discrete dislocation results during unloading, showing a pronounced Bauschinger effect. None of these features are captured by standard local plasticity theories.

Molecular structure of the lecithin ripple phase

Abstract: Molecular dynamics simulations of lecithin lipid bilayers in water as they are cooled from the liquid crystalline phase show the spontaneous formation of rippled bilayers. The ripple consists of two domains of different length and orientation, connected by a kink. The organization of the lipids in one domain of the ripple is found to be that of a splayed gel; in the other domain the lipids are gel-like and fully interdigitated. In the concave part of the kink region between the domains the lipids are disordered. The results are consistent with the experimental information available and provide an atomic-level model that may be tested by further experiments.

Bending of a single crystal: discrete dislocation and nonlocal crystal plasticity simulations

Abstract: We have recently proposed a nonlocal continuum crystal plasticity theory that is based on a statistical-mechanics description of the collective behaviour of dislocations. Kinetic equations for the dislocation density fields have been derived from the equation of motion of individual dislocations and have been coupled to a continuum description of single slip. Dislocation nucleation, the material resistance to dislocation glide and dislocation annihilation are included in the formulation. The theory is applied, in this paper, to the problem of bending of a single-crystal strip in plane strain, using parameter values obtained previously from fitting to discrete dislocation results of a different boundary value problem. A numerical solution of the problem is obtained using a finite element method. The bending moment versus rotation angle and the evolution of the dislocation structure are analysed for different orientations and specimen sizes with due consideration of the role of geometrically necessary dislocations. The results are compared to those of discrete dislocation simulations of the same problem. Without any additional fitting of the parameters, the continuum theory is able to describe the dependence on slip plane orientation and on specimen size.

Gromacs 4.5

Abstract: Motivation: Molecular simulation has historically been a low-throughput technique, but faster computers and increasing amounts of genomic and structural data are changing this by enabling large-scale automated simulation of, for instance, many conformers or mutants of biomolecules with or without a range of ligands. At the same time, advances in performance and scaling now make it possible to model complex biomolecular interaction and function in a manner directly testable by experiment. These applications share a need for fast and efficient software that can be deployed on massive scale in clusters, web servers, distributed computing or cloud resources. Results: Here, we present a range of new simulation algorithms and features developed during the past 4 years, leading up to the GROMACS 4.5 software package. The software now automatically handles wide classes of biomolecules, such as proteins, nucleic acids and lipids, and comes with all commonly used force fields for these molecules built-in. GROMACS supports several implicit solvent models, as well as new free-energy algorithms, and the software now uses multithreading for efficient parallelization even on low-end systems, including windows-based workstations. Together with hand-tuned assembly kernels and state-of-the-art parallelization, this provides extremely high performance and cost efficiency for high-throughput as well as massively parallel simulations. Availability: GROMACS is an open source and free software available from http://www.gromacs.org. Contact: erik.lindahl@scilifelab.se Supplementary information:Supplementary data are available at Bioinformatics online.

The MARTINI Coarse-Grained Force Field: Extension to Proteins

Abstract: Many biologically interesting phenomena occur on a time scale that is too long to be studied by atomistic simulations. These phenomena include the dynamics of large proteins and self-assembly of biological materials. Coarse-grained (CG) molecular modeling allows computer simulations to be run on length and time scales that are 2–3 orders of magnitude larger compared to atomistic simulations, providing a bridge between the atomistic and the mesoscopic scale. We developed a new CG model for proteins as an extension of the MARTINI force field. Here, we validate the model for its use in peptide-bilayer systems. In order to validate the model, we calculated the potential of mean force for each amino acid as a function of its distance from the center of a dioleoylphosphatidylcholine (DOPC) lipid bilayer. We then compared amino acid association constants, the partitioning of a series of model pentapeptides, the partitioning and orientation of WALP23 in DOPC lipid bilayers and a series of KALP peptides in dimyris...

Oxidized arachidonic and adrenic PEs navigate cells to ferroptosis

Abstract: Enigmatic lipid peroxidation products have been claimed as the proximate executioners of ferroptosis-a specialized death program triggered by insufficiency of glutathione peroxidase 4 (GPX4). Using quantitative redox lipidomics, reverse genetics, bioinformatics and systems biology, we discovered that ferroptosis involves a highly organized oxygenation center, wherein oxidation in endoplasmic-reticulum-associated compartments occurs on only one class of phospholipids (phosphatidylethanolamines (PEs)) and is specific toward two fatty acyls-arachidonoyl (AA) and adrenoyl (AdA). Suppression of AA or AdA esterification into PE by genetic or pharmacological inhibition of acyl-CoA synthase 4 (ACSL4) acts as a specific antiferroptotic rescue pathway. Lipoxygenase (LOX) generates doubly and triply-oxygenated (15-hydroperoxy)-diacylated PE species, which act as death signals, and tocopherols and tocotrienols (vitamin E) suppress LOX and protect against ferroptosis, suggesting a homeostatic physiological role for vitamin E. This oxidative PE death pathway may also represent a target for drug discovery.

Improved Parameters for the Martini Coarse-Grained Protein Force Field

Abstract: The Martini coarse-grained force field has been successfully used for simulating a wide range of (bio)molecular systems. Recent progress in our ability to test the model against fully atomistic force fields, however, has revealed some shortcomings. Most notable, phenylalanine and proline were too hydrophobic, and dimers formed by polar residues in apolar solvents did not bind strongly enough. Here, we reparametrize these residues either through reassignment of particle types or by introducing embedded charges. The new parameters are tested with respect to partitioning across a lipid bilayer, membrane binding of Wimley–White peptides, and dimerization free energy in solvents of different polarity. In addition, we improve some of the bonded terms in the Martini protein force field that lead to a more realistic length of α-helices and to improved numerical stability for polyalanine and glycine repeats. The new parameter set is denoted Martini version 2.2.