Ilia A. Solov’yov

Solvent driving force ensures fast formation of a persistent and well-separated radical pair in plant cryptochrome.

The photoreceptor protein cryptochrome is thought to host, upon light absorption, a radical pair that is sensitive to very weak magnetic fields, endowing migratory birds with a magnetic compass sense. The molecular mechanism that leads to formation of a stabilized, magnetic field sensitive radical pair has despite various theoretical and experimental efforts not been unambiguously identified yet. We challenge this unambiguity through a unique quantum mechanical molecular dynamics approach where we perform electron transfer dynamics simulations taking into account the motion of the protein upon the electron transfer. This approach allows us to follow the time evolution of the electron transfer in an unbiased fashion and to reveal the molecular driving force that ensures fast electron transfer in cryptochrome guaranteeing formation of a persistent radical pair suitable for magnetoreception. We argue that this unraveled molecular mechanism is a general principle inherent to all proteins of the cryptochrome/photolyase family and that cryptochromes are, therefore, tailored to potentially function as efficient chemical magnetoreceptors.

Studying chemical reactions in biological systems with MBN Explorer: implementation of molecular mechanics with dynamical topology

AbstractThe concept of molecular mechanics force field has been widely accepted nowadays for studying various processes in biomolecular systems. In this paper, we suggest a modification for the standard CHARMM force field that permits simulations of systems with dynamically changing molecular topologies. The implementation of the modified force field was carried out in the popular program MBN Explorer, and, to support the development, we provide several illustrative case studies where dynamical topology is necessary. In particular, it is shown that the modified molecular mechanics force field can be applied for studying processes where rupture of chemical bonds plays an essential role, e.g., in irradiation- or collision-induced damage, and also in transformation and fragmentation processes involving biomolecular systems.Graphical abstract

Multiscale description of avian migration: from chemical compass to behaviour modeling

Despite decades of research the puzzle of the magnetic sense of migratory songbirds has still not been unveiled. Although the problem really needs a multiscale description, most of the individual research efforts were focused on single scale investigations. Here we seek to establish a multiscale link between some of the scales involved, and in particular construct a bridge between electron spin dynamics and migratory bird behaviour. In order to do that, we first consider a model cyclic reaction scheme that could form the basis of the avian magnetic compass. This reaction features a fast spin-dependent process which leads to an unusually precise compass. We then propose how the reaction could be realized in a realistic molecular environment, and argue that it is consistent with the known facts about avian magnetoreception. Finally we show how the microscopic dynamics of spins could possibly be interpreted by a migrating bird and used for the navigational purpose.

Glutamate Water Gates in the Ion Binding Pocket of Na + Bound Na + , K + -ATPase

The dynamically changing protonation states of the six acidic amino acid residues in the ion binding pocket of the Na+, K+ -ATPase (NKA) during the ion transport cycle are proposed to drive ion binding, release and possibly determine Na+ or K+ selectivity. We use molecular dynamics (MD) and density functional theory (DFT) simulations to determine the protonation scheme of the Na+ bound conformation of NKA. MD simulations of all possible protonation schemes show that the bound Na+ ions are most stably bound when three or four protons reside in the binding sites, and that Glu954 in site III is always protonated. Glutamic acid residues in the three binding sites act as water gates, and their deprotonation triggers water entry to the binding sites. From DFT calculations of Na+ binding energies, we conclude that three protons in the binding site are needed to effectively bind Na+ from water and four are needed to release them in the next step. Protonation of Asp926 in site III will induce Na+ release, and Glu327, Glu954 and Glu779 are all likely to be protonated in the Na+ bound occluded conformation. Our data provides key insights into the role of protons in the Na+ binding and release mechanism of NKA.

Atomic Clusters and Nanoparticles

MBN Explorer is suitable for computer simulations of structure and dynamics of atomic and molecular clusters (sometimes also called nanoparticles (NPs) or nanocrystals) of different materials, e.g., metal, semiconductor, dielectric, etc. The sizes of these systems could be varied from a few atoms up to a few millions of atoms. Possible simulation tasks include structure analysis and optimization, various thermal effects, mechanical properties, nanoscale phase transitions. MBN Explorer is especially useful for studying large clusters and associated processes. Special attention is paid to the clusters on surfaces.

Activation of the DNA-repair mechanism through NBS1 and MRE11 diffusion

The non-homologous end joining of a DNA double strand break is initiated by the MRE11-NBS1-RAD50 complex whose subunits are the first three proteins to arrive to the breakage site thereby making the recruitment time of MRE11, NBS1 and RAD50 essential for cell survival. In the present investigation, the nature of MRE11 and NBS1 transportation from the cytoplasm to the nucleus, hosting the damaged DNA strand, is hypothesized to be a passive diffusive process. The feasibility of such a mechanism is addressed through theoretical and computational approaches which permit establishing the characteristic recruitment time of MRE11 and NBS1 by the nucleus. A computational model of a cell is constructed from a set of biological parameters and the kinetic Monte Carlo algorithm is used to simulate the diffusing MRE11 and NBS1 particles as a random walk process. To accurately describe the experimented data, it is discovered that MRE11 and NBS1 should start diffusion from significantly different starting positions which suggests that diffusion might not be the only transport mechanism of repair protein recruitment to the DNA break.

Absorption Spectra of FAD Embedded in Cryptochromes

The magnetic compass sense utilized by migratory birds for long-distance navigation functions only once light of a certain wavelength is present. This piece of evidence fits partially with the popular hypothesis of chemical magnetoreception in cryptochrome proteins, located in the bird retina. According to this hypothesis a magnetosensitive radical pair is produced after photoexcitation of an FAD cofactor inside cryptochrome, and as such the absorption properties of FAD are of crucial importance for cryptochrome activation. However, we reveal that absorption spectra of FAD show very little variation between six different cryptochromes, suggesting that the electronic transitions are barely affected by the chemical differences in the proteins. This conclusion hints on the presence of a secondary photoreceptor or cofactor that could be necessary to explain green-light-activated magnetoreception in birds.

Introduction to Computational Meso-Bio-Nano (MBN) Science and MBN E xplorer

This chapter presents an introduction to the Meso-Bio-Nano Science—a novel field of interdisciplinary research. It introduces the major ideas, focuses and goals of Meso-Bio-Nano Science, objects and systems of study, and explains how they are linked to a wide range of applications in Physics, Chemistry, Biology, Material Science, and related industries. The chapter gives a short overview of the major computational approaches exploited in the field. Significant part of the chapter is devoted to MesoBioNano Explorer (MBN Explorer)—a multi-purpose software package for advanced multiscale simulations of complex molecular structure and dynamics. The chapter presents the unique positions of MBN Explorer in the field of MesoBioNano Science, based on the capabilities of the software package to simulate efficiently structure and dynamics of a broad range of very different complex molecular systems with the sizes ranging from the atomic up to the mesoscopic scales. The chapter introduces the main features of MBN Explorer and the areas of its application. The chapter introduces also MBN Studio—a special multi-task toolkit for MBN Explorer, which enables construction of input files, simple start of simulations with MBN Explorer, as well as visualisation and analysis of the results obtained.

Theoretical Approaches for Multiscale Computer Simulations

This chapter presents a summary of main theoretical methods that are implemented in MBN Explorer. The significant part of the methodologies outlined is devoted to the classical molecular dynamics, which is based on the concept of molecular force fields. A variety of different force fields is introduced and their applicability to the description of molecular systems of different kind is discussed. Special attention is paid to biomolecular systems. The key algorithms (integrators, linked cell approach, Ewald summation, etc.), as well the essential aspects of the computational realisation of molecular dynamics (thermostats, boundary conditions, etc.) are elaborated in details. The basic ideas towards the multiscale description of MBN systems by means of kinetic Monte Carlo approach and the irradiation driven molecular dynamics are introduced and discussed.

Novel and Emerging Technologies

MBN Explorer is a very useful and powerful tool for the exploration of the challenging interdisciplinary research problems. Often such problems arise in connection with the development of new technologies. There are many such examples, in which simulations performed with the use of MBN Explorer are being highly demanded. This Chapter presents several such exemplar cases. They concern (i) the construction of novel light sources based on charged particles channeling in crystalline undulators, (ii) the simulation of nanoscopic molecular processes playing the key role in the course of ion-beam cancer therapy (IBCT) treatment, and (iii) Focused Electron Beam Induced Deposition (FEBID)—a novel technology that is being used for improving the manufacturing of specific nano-devices through better material control and higher spatial resolution of the deposition process.