APPLICATIONS: Physicochemical Biology

Modeling mechanisms of photochemical processes in photoreceptor and fluorescent proteins


Khrenova Maria
Moscow State Uiversity

DRIVER: Studying mechanisms of functioning of fluorescent proteins, flavin containing photoreceptor proteins and bacterial photosystem

STRATEGY: Development and application of methods of computer molecular modeling, including combined method of quantum mechanics/ molecular mechanics and modern approaches of quantum chemistry, for properties calculations of photoreceptor proteins and their chromophores

OBJECTIVE: Establishment of mechanisms of functioning of fluorescent proteins, flavin containing photoreceptor proteins and bacterial using combined method of quantum mechanics/ molecular mechanics and modern methods of quantum chemistry of high level of accuracy

IMPACT: Prediction of new fluorescent and photoreceptor proteins with the suggested properties, on the basis of mechanisms established in the project

USAGE: biosensor technologies, life sciences

AREA: Structure and Dynamics of Atomic-Molecular Systems, Physicochemical Biology



Multiscale molecular simulations of membrane proteins


Shaitan Konstantin
Moscow State Uiversity

DRIVER: Understanding functioning of membrane proteins at molecular level

STRATEGY: Use multi-scale molecular modeling techniques

OBJECTIVE: Study of membrane protein dynamics and its dependence on internal and external factors

IMPACT: Understanding the fundamentals of living systems, drug design

USAGE: Pharmacology, medicine

AREA: Physicochemical Biology



Molecular modeling of biochemical and biophysical processes in cholinesterases and development of new drugs interacting with them


Lushchekina Sofia
Moscow State Uiversity

DRIVER: Cholinesterases play crucial role in human physiology. Detailed understanding of their biochemical and biophysical properties is crucial for better understanding of human body metabolism. Cholinesterases are involved in development of several serious conditions (Alzheimer disease, myasthenia) and as such are targets for drug treatment of these diseases. Also there are targets of poisonous compounds and better understanding of their functioning mechanism is necessary for development of protective measures.

STRATEGY: Molecular modeling of dynamics and conformational changes in the enzymes protein molecules, study of energy profiles of their interactions with inhibitors and substrates by means of molecular docking, molecular dynamics, quantum mechanics, combined quantum mechanics and molecular mechanics, combined quantum mechanics and molecular dynamics methods.

OBJECTIVE: New information about processes in biological systems and their interactions with different chemical compounds – poisons and drugs. Development of new drugs and protective agents

IMPACT: Extension of basic knowledge for biochemical and biomedical research. Development and implementation of new drugs

USAGE: Pharmacology and medicine. Anti-Alzheimer disease and anti-myasthenic drugs, protective agents for aviation (passengers, crew, land personnel) against aerotoxic syndrome.

AREA: Physicochemical Biology



Study of substrate specificity of glycosidase superfamily enzymes using bioinformatics and molecular modeling


Kirilin Evgeny
Moscow State Uiversity

DRIVER: To evaluate the influence of amino acid positions on substrate specificity of glycosidase superfamily enzymes.

STRATEGY: Using bioinformatic analysis method to identify subfamily specific positions. Using molecular modeling (docking, molecular dynamics) software to evaluate the influence of found positions on proteins specificity.

OBJECTIVE: To identify and evaluate conserved positions that probably has a direct role in function common for the entire family, and subfamily specific positions (SSPs) — conserved only within protein subfamilies, but different between them thus potentially responsible for function discrimation between groups.

IMPACT: With the knowledge of functional positions the methods of protein engeneering could be applied to change substrate specificity of glycosidases.

USAGE: Pharmacology, biotechnology

AREA: Physicochemical Biology



Fullerene and its derivatives interactions with biomembranes: a molecular dynamics simulation study


Bozdaganian Marine
Moscow State Uiversity

DRIVER: Analyze penetration of the different fullerenes into the membrane

STRATEGY: Calculate potential of mean forces for different fullerenes with membranes

OBJECTIVE: Predict fullerenes toxicity

IMPACT: scientific

USAGE: Science: prediction of dangerous fullerene derivatives

AREA: Physicochemical Biology



Computer simulations of amyloid-like fibrils


Shaitan Aleksey
Moscow State Uiversity

DRIVER: Understanding structure and properties of artificial amyloid-like fibrils for bionanotechnology applications

STRATEGY: Employ multiscale atomistic computer simulations based on molecular dynamics simulations

OBJECTIVE: Determine the structure and properties of specific amyloid-like fibrils used to enhance retroviral transfection.

IMPACT: Understanding the structure and mechanisms of action of the fibrils

USAGE: Biotechnology, genetic engineering

AREA: Physicochemical Biology, High Molecular Weight Compounds



Research of raft systems using computer simulations


Bozdaganian Marine
Moscow State Uiversity

DRIVER: Analysis of two monolayers of the raft

STRATEGY: Do and test model system raft in biomembrane-water and study structural properties

OBJECTIVE: Calculate free energy of shift

IMPACT: scientific

USAGE: membrane biophysics

AREA: Physicochemical Biology



Investigation of the two-component sensors of Bacteria and Archea by Molecular Dynamics


Orehov Philipp
Moscow State Uiversity

DRIVER: molecular dynamics of a dimer of the photosensor of archea Natromonas pharaonis (NpHtrII); molecular dynamics of the trimer-of-dimers of NpHtrII

STRATEGY: classical MD approach, coarse-grained MD (MARTINI force field

OBJECTIVE: Understanding of methylation in functioning of bacterial receptors; determination of the functional and structural role of HAMP domains in signal propagation

IMPACT: design an adequate model for functioning of bacterial and archeal receprotrs in membrane clusters accounting the all of available to the moment experimental data

USAGE: comprehension of fundamental basis of function of bacterial and archeal receptors

AREA: Physicochemical Biology



Studies on the structure-functional determinants of the Alzheimer disease


Paulshakov Vladimir
Moscow State Uiversity

DRIVER: Understanding the molecular basis of the Alzheimer disease

STRATEGY: Molecular dynamics, quantum mechanics, hybrid QM/MM method

OBJECTIVE: Determining the structure of the metal binding domain of both pathological and non-pathological forms of beta-amyloid in complex with metal ions.

IMPACT: Scientific. In long term commercial effect may appear.

USAGE: life science, fundamental medicine

AREA: Fundamental Medicine and Phisiology, Physicochemical Biology



Bioinformatics analysis of enzyme superfamilies to study protein structure-function relationships and design of novel improved biocatalysts.


Suplatov Dmitry
Moscow State Uiversity

DRIVER: To develop comprehensive methodology for exploration of protein mechanisms of action and protein design using computational and experimental methods of bioinformatics, molecular modelling, biochemistry and enzymology.

STRATEGY: The methods of systems biology and bioinformatic analysis will be used for identification of amino acid positions within protein structure that are able to change specified protein functioning when modified. Obtained data will be used to design in silico library of mutant proteins that will be evaluated and screened by computational chemistry methods to predict catalytic properties of mutants with the use of specified functioning criteria of enzyme/substrate complexes. Selected promising mutants will be synthetized and characterized by experimentalists.

OBJECTIVE: To study the molecular mechanisms responsible for the correspondence between protein structure and its functioning.

IMPACT: Accumulated knowledge and developed methods will be used to design improved biocatalysts by directed change of their structure.

USAGE: Pharmacology, biotechnology, chemical industry

AREA: Physicochemical Biology



Mathematical modeling of mitotic cell division at molecular level in order to find new targets for anticancer treatment


Zaharov Pavel
Center for Theoretical Problems of Physicochemical Pharmacology of RAS

DRIVER: Study of molecular mechanisms of protein interactions in mitotic system

STRATEGY: Integration of experimental data from mechano-molecular system of cell division using methods of molecular dynamics and coarse grained models for proteins

OBJECTIVE: Creation new type of anticancer drugs

IMPACT: Scientific: new information about cell division. Commercial: new effective anti-cancer drugs. The market for such medicines is hundreds billions of dollars. Social: increasing length of the life for millions of people

USAGE: Pharmacology, medicine, molecular and cell biology

AREA: Medical Physics, Structure and Dynamics of Atomic-Molecular Systems, Physicochemical Biology



Modeling of the chlorosome optical linear response


Pishchalnikov Roman
Prokhorov General Physics Institute of RAS

DRIVER: To get a good fit of the experimental and calculated data of the absorption, circular and linear dichroism.

STRATEGY: Using the parallel programming to speed up the ralaxation exciton rates calculation.

OBJECTIVE: To get a good fit of the experimental and calculated data of the absorption, circular and linear dichroism.

IMPACT: Examination of the hypothesys of the chlorosome light-harvesting complex organization

USAGE: biophysics, biochemestry

AREA: Informatics, Optics and Quantum Electronics, Physicochemical Biology



Computer modeling of supramolecular complexes of polyelectrolytes with biological membranes


Gurtovenko Andrey
Institute of Macromolecular Compounds of RAS

DRIVER: The project focuses on molecular mechanisms behind interactions between natural and synthetic polyelectrolytes with biological membranes. Such interactions are important for bionanotechnology as well as for biological processes in cell nuclei. In particular, synthetic polycations are widely used for modulating the structure of biomembranes. Lipid bilayer membranes are of increasing interest due to their potential to serve as delivery vectors for DNA strands which are essentially natural polyanions. Despite the importance of the polyelectrolyte-membrane interactions the molecular mechanisms of such interactions and the microscopic structure of supramolecular polyelectrolyte-membrane complexes remain largely unknown mostly due to limitations of existing experimental techniques. In this project we will employ the state-of-the-art computer modeling along with computational models of high (atomistic) resolution to get insight into the interactions of anionic DNA molecules and synthetic cationic polymers with model phospholipid membranes.

STRATEGY: In order to unlock molecular mechanisms of the polyelectrolyte-membrane interactions, we will use the state-of-the-art computer simulations. In particular, the molecular dynamics techniques will be used; this method is nowadays one of the standard tools for studying complex biomolecular and polymer systems. To describe polyelectrolytes (synthetic cationic polymers and native polyanionic DNA molecules) and phospholipid model membranes we will employ computational models of high (atomistic) resolution, in which the chemical structure of compounds is explicitly accounted for. This allows us to obtain microscopic details of adsorption processes, the details that are not accessible for most experimental methods. The usage of atomistic models and relatively large size of the polyelectrolyte-membrane systems will require considerable multi-CPU computational resources. It should be emphasized that the project leader has extensive experience of computer modeling of biomolecular and polymer systems, which can be seen through high scientific impact of his publications (1500 citations, H-index 24).

OBJECTIVE: The project focuses on a systematic study of adsorption of various types of polyelectrolytes on biomembranes. DNA polyanions and synthetic polycations (such as polyethylenimine and poly-L-lysine) will be considered as polyelectrolytes. The main objective of the project is to establish possible mechanisms behind a controlled manipulation of permeability of biomembranes due to adsorption of polyelectrolytes. The structure and stability of supramolecular complexes "DNA-lipids" which are used for gene delivery will be also of special interest.

IMPACT: The supramolecular complexes of natural and synthetic polyelectrolytes with biological membranes play a crucial role in biotechnology, medicine and biology, thereby making the present research project timely and important. The results will stimulate further development novel, antibacterial agents as well as new effective liposome-based vehicles for DNA delivery. Most of the problems mentioned in the project have not been handled yet with the use of atomic-scale computer modeling. Therefore, a successful implementation of the project will produce a number of pioneering contributions into the very promising area of biological and biomedical research.

USAGE: The results of the project can be used in medicine, biotechnology, pharmacy, and biology.

AREA: High Molecular Weight Compounds, Physical Chemistry, Physicochemical Biology



Study of structure and function of M2 protein using molecular dynamics simulation method.


Nicolini Claudio
Moscow State Uiversity

DRIVER: Building the model of M2 protein inside the membrane, studying of dynamics characteristics of the system. Studying of interaction of M2 protein with different ligands.

STRATEGY: For obtaining nice results it's suggested to use improved NMR structures of the protein M2. Also we include in the progect studying of interaction of our protein with already certified antiviral drugs.

OBJECTIVE: Searcing for new blocators of M2 channel, creating new potential drugs.

IMPACT: Scientific: new articles about structure and functions of M2 protein. Commersial: creating new potential drugs against influenza virus.

USAGE: Results of the progect can shed the light on functions of the protein and new blocators of the M2 channel. This knowledge is useful for pharma industry.

AREA: Physicochemical Biology



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