A5074996596- Photoreceptor and optogenetics research
- Photosynthetic Processes and Mechanisms
- Advanced Chemical Physics Studies
- Protein Structure and Dynamics
- Advanced Fluorescence Microscopy Techniques
- Enzyme Structure and Function
- Spectroscopy and Quantum Chemical Studies
- Computational Drug Discovery Methods
- Inorganic Fluorides and Related Compounds
- Cholinesterase and Neurodegenerative Diseases
- Photochemistry and Electron Transfer Studies
- Light effects on plants
- DNA and Nucleic Acid Chemistry
- bioluminescence and chemiluminescence research
- Biochemical and Molecular Research
- Molecular Spectroscopy and Structure
- Photochromic and Fluorescence Chemistry
- RNA and protein synthesis mechanisms
- Pesticide Exposure and Toxicity
- Chemical Reaction Mechanisms
- Molecular Junctions and Nanostructures
- nanoparticles nucleation surface interactions
- Electron Spin Resonance Studies
- Enzyme function and inhibition
- Quantum, superfluid, helium dynamics
Lomonosov Moscow State University
2016-2025
Institute of Biochemical Physics NM Emanuel
2016-2025
Moscow State University
2009-2024
Russian Academy of Sciences
2006-2015
University of Southern California
2009-2010
Max Planck Institute for Medical Research
2010
University of Helsinki
2002-2009
Computing Center
2002-2006
National Cancer Institute
2002-2006
A N Bach Institute of Biochemistry
2006
The unique properties of green fluorescent protein (GFP) have been harnessed in a variety bioimaging techniques, revolutionizing many areas the life sciences. Molecular-level understanding underlying photophysics provides an advantage design new proteins (FPs) with improved properties; however, because its complexity, aspects GFP photocycle remain unknown. In this Account, we discuss computational studies FPs and their chromophores that provide qualitative insights into mechanistic details...
We present the results of quantum chemical calculations transition energies and conical intersection points for two lowest singlet electronic states green fluorescent protein chromophore, 4′-hydroxybenzylidene-2,3-dimethylimidazolinone, in vicinity its cis conformation gas phase. Four protonation i.e., anionic, neutral, cationic, zwitterionic, were considered. Energy differences computed by perturbatively corrected complete active space self-consistent field (CASSCF)-based approaches at...
We present the results of quantum chemical calculations electronic properties anionic form green fluorescent protein chromophore in gas phase. The vertical detachment energy is found to be 2.4−2.5 eV, which below strongly absorbing ππ* state at 2.6 eV. excitation lowest triplet around 1.9 photodetachment continuum. Thus, bright singlet a resonance embedded continuum, whereas regular bound state. Based on our estimation energy, we attribute minor feature action spectrum as due transition....
The effect of the protein environment on electronic structure green fluorescent (GFP) chromophore is investigated by QM/MM (quantum mechanics/molecular mechanics) calculations. has very small excitation energy bright absorbing and lowest triplet states anionic GFP chromophore, deprotonated 4-hydroxybenzylidene-2,3-dimethylimidazolinone (HBDI) anion, however, it increases vertical detachment from 2.5 eV (gas-phase HBDI anion) to 5.0 (solvated protein). We also possible existence...
Organophosphorus agents (OPs) are irreversible inhibitors of acetylcholinesterase (AChE). OP poisoning causes major cholinergic syndrome. Current medical counter-measures mitigate the acute effects but have limited action against OP-induced brain damage. Bioscavengers appealing alternative therapeutic approach because they neutralize OPs in bloodstream before reach physiological targets. First generation bioscavengers stoichiometric bioscavengers. However, neutralization requires...
Abstract The mechanism of the hydrolysis reaction guanosine triphosphate (GTP) by protein complex Ras–GAP (p21 ras – p120 GAP ) has been modeled quantum mechanical—molecular mechanical (QM/MM) and ab initio calculations. Initial geometry configurations have prompted atomic coordinates a structural analog (PDBID:1WQ1). It is shown that minimum energy path consistent with an assumption two‐step chemical transformations. At first stage, unified motion Arg789 GAP, Gln61, Thr35 Ras, lytic water...
Abstract The hydrolysis reaction of guanosine triphosphate (GTP) by p21 ras (Ras) has been modeled using the ab initio type quantum mechanical–molecular mechanical simulations. Initial geometry configurations have prompted atomic coordinates crystal structure (PDBID: 1QRA) corresponding to prehydrolysis state Ras in complex with GTP. Multiple searches minimum energy consistent hydrogen bond networks performed, resulting a series stationary points on potential surface for intermediates and...
Structures and optical spectra of the green fluorescent protein (GFP) forms along proton transfer route A→I→B are characterized by first-principles calculations. We show that in ground electronic state structure representing wild-type (wt) GFP with neutral chromophore (A-form) is lowest energy, whereas systems anionic (B- I-forms) about 1 kcal/mol higher. In S65T mutant, structures significantly lower energy than chromophore. The role nearby amino acid residues chromophore-containing pocket...
Molecular mechanisms of the hydrolysis guanosine triphosphate (GTP) to diphosphate (GDP) and inorganic phosphate (Pi) by Ras·GAP protein complex are fully investigated using modern modeling tools. The previously hypothesized stages cleavage phosphorus–oxygen bond in GTP formation imide form catalytic Gln61 from Ras upon creation Pi confirmed higher-level quantum-based calculations. steps enzyme regeneration modeled for first time, providing a comprehensive description cycle. It is found that...
We report the first complete theoretical description of chain elementary reactions resulting in chromophore maturation green fluorescent protein (GFP). All reaction steps including cyclization, dehydration, and oxidation are characterized at uniform quantum mechanics/molecular mechanics (QM/MM) computational level using density functional theory subsystems. Starting from a structure wild-type with noncyclized Ser65-Tyr66-Gly67 tripeptide, we modeled cyclization dehydration reactions. then...
Remarkable success in engineering novel efficient biomarkers based on fluorescent and photoactive proteins provokes a question of whether computational modeling their properties can contribute to this important field. In Feature Article, we analyze selected papers devoted computer simulations three types systems: the green protein its derivatives, flavin-binding proteins, phytochrome domains. The main emphasis is structures, optical spectra, chemical reactions chromophore-containing pockets....
We report the results of computational modeling reactions SARS-CoV-2 main protease (MPro) with four potential covalent inhibitors. Two them, carmofur and nirmatrelvir, have shown experimentally ability to inhibit MPro. other compounds, X77A X77C, were designed computationally in this work. They derived from structure X77, a non-covalent inhibitor forming tight surface complex modified X77 by introducing warheads capable reacting catalytic cysteine residue MPro active site. The reaction...
Theoretical and matrix-isolation studies of intermolecular complexes HXeOH with water molecules are presented. The structures possible decomposition routes the HXeOH-(H(2)O)(n)(n = 0, 1, 2, 3) analyzed theoretically. It is concluded that decay these metastable species may proceed through bent transition states (TSs), leading to global minima on respective potential energy surfaces, Xe + (H(2)O)(n+1). barrier heights 39.6, 26.6, 11.2, 0.4 kcal/mol for n 3. in larger clusters computationally...
The intrinsic chemical reaction of adenosine triphosphate (ATP) hydrolysis catalyzed by myosin is modeled using a combined quantum mechanics and molecular (QM/MM) methodology that achieves near ab initio representation the entire model. Starting with coordinates derived from heavy atoms crystal structure (Protein Data Bank ID code 1VOM) in which bound to ATP analog ADP.VO(4)(-), minimum-energy path found for transformation + H(2)O --> ADP P(i) characterized two distinct events: (i) low...
Cancer-associated point mutations in Ras, particular, at glycine 12 and 13, affect the normal cycle between inactive GDP-bound active GTP-bound states. In this work, role of G12V G13V replacements GAP-stimulated intrinsic GTP hydrolysis reaction Ras is studied using molecular dynamics (MD) simulations with quantum mechanics/molecular mechanics (QM/MM) potentials. A model system was constructed by motifs relevant crystal structure (Protein Data Bank entry 1WQ1). QM/MM optimization geometry...
Development and applications of a new approach to hybrid quantum mechanical molecular (QM/MM) theory based on the effective fragment potential (EFP) technique for modeling properties reactivity large systems biochemical significance are described. It is shown that restriction frozen internal coordinates fragments in original formulation (Gordon, M. S.; Freitag, A.; Bandyopadhyay, P.; Jensen, J. H.; Kairys, V.; Stevens, W. Phys. Chem. A 2001, 105, 293) can be removed by introducing set small...
The mechanism of the hydrolysis reaction unprotonated methyl triphosphate (MTP) ester in water clusters has been modeled. effective fragment potential based quantum mechanical-molecular mechanical (QM/MM) approach applied simulations. It is shown that minimum energy path consistent with an assumption a two-step dissociative-type process similar to case guanosine (GTP) Ras-GAP protein complex (Grigorenko, B. L.; Nemukhin, A. V.; Topol, I. A.; Cachau, R. E.; Burt, S. K. Proteins: Struct.,...
The proposed mechanisms of photoinduced reactions in the blue light using flavin chromophore photoreceptor proteins are primarily based on results X-ray crystallography and spectroscopy studies. Of particular value observed band shifts optical vibrational spectra upon formation signaling (light-induced) state. However, same set experimental data has given rise to contradictory interpretations suggesting different structures dark states. To verify specific mechanism light-induced changes...
We present quantum chemical calculations of the properties anionic form green fluorescent protein (GFP) chromophore that can be directly compared to results experimental measurements: cis-trans isomerization energy profile in water. Calculations pathway gas phase and water reveal a problematic behavior density functional theory scaled opposite-spin-MP2 due multiconfigurational character wave function at twisted geometries. The solvent effects treated with continuum solvation models, as well...
Amide-imide tautomerization presents a pervasive class of chemical transformations in organic chemistry natural compounds. In this Perspective, we describe two distinctively different protein systems, which the amide-imide glutamine side chain takes place enzymatic or photochemical reactions. First, hydrolysis guanosine triphosphate (GTP) catalyzed by Ras-GAP complex suggests occurrence imide tautomer reaction intermediates. Second, photoexcitation flavin-binding domains (BLUFs) initiates...
This work explores the level of transparency in reporting details computational protocols that is required for practical reproducibility quantum mechanics/molecular mechanics (QM/MM) simulations. Using reaction an essential SARS-CoV-2 enzyme (the main protease) with a covalent inhibitor (carmofur) as test case chemical reactions biomolecules, we carried out QM/MM calculations to determine structures and energies reactants, product, transition state/intermediate using analogous models...