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Main Results
2004-2010. Self-organization of E.coli oligomeric chaperon system GroEL/GroES was been studied in vitro.
It was shown that self-organization of oligomeric GroES does not require any ligands or additional factors.
However, the oligomerization of GroEL monomers occurs only in the presence of Mg ions, ATP and, at low GroEL
concentrations (less than 0.1 mg/ml) of co-chaperon GroES also. A scheme of the assembly of the chaperon system
GroEL/GroES in vitro, which is possibly realized in vivo also, has been proposed.
2008-2010. We demonstrated a possibility to calculate the rate constants of protein unfolding and entropic
and enthalpic components of these constants from the calorimetric curves of their non-equilibrium melting.
2008-2010. A method for optimization of combinations of substitution matrices and pseudopo-tentials has been
developed; it is effective for aligning protein primary and tertiary structures of weakly homologous protein chains.
2007-2010. We established a dependence of amyloid formation on stability of the apomyoglobin's native state:
stable native state produces neither amyloids nor aggregates; somewhat destabilized native state forms amyloids,
and strongly destabilized native state produces aggregates.
2006-2009. A three-dimensional phase diagram of apomyoglobin's states is obtained in coordinates pH - denaturant
concentration - temperature. It shows three phase states of the protein (native, intermediate, and coil), and
no cooperative transitions between various forms of the intermediate state.
2005-2009. We developed a multi-factor approach to analyze experimental data on multiphase folding kinetics
of a protein, whose first intermediate state forms within the instrumental dead time, and to quite accurately obtain
the rate constant of its next state formation.
2000-2009. Interaction of various non-native proteins with the E.coli chaperon system GroEL/GroES was studied.
It is shown that electrostatic, as well as hydrophobic forces are important for the formation of the binary complex
GroEL·protein. A new model the GroEL - assisted protein folding is proposed; it assumes that protein folding occurs
in a free state, out of the complex with GroEL/GroES chaperon, which prevents the protein aggregation only.
2004-2009. It is shown that the side chain interactions in the apomyoglobin folding intermediate (molten globule)
are not that strong even for conserved a.a. residues (accounting for 30% of interactions in the native protein),
while for non-conserved residues of B, C, D, E helices they are vanishingly small.
2004-2009. It is shown that the increment of conserved a.a. residues of A, G, H helices to stability of
the apomyoglobin folding intermediate is higher than that of non-conserved residues, while the major increment
to stability of the main transition state at the apomyoglobin folding pathway (corresponding to the native state
formation from the intermediate) is, on the contrary, provided by non-conserved residues of B, D, E helices.
2008. It is shown that positions of the Efimov's "root structural motifs" in 3D protein struc-tures is highly
correlated with positions of the protein folding nuclei.
2007-2008. It is shown that many-atom Van Der Waals interactions lead to specific, direction-sensitive interactions
of covalent bonds.
2004-2006. New methods for prediction of "natively-unfolded" and amyloidigenic regions of protein chains from their amino acid sequences have been developed.
2003-2004. An algorithm calculating the protein folding rate from its amino acid sequence is developed.
2003. A bioluminescence energy transfer-based method for registration of protein-protein interactions at extremely low protein concentrations is developed.
2000-2004. It has been shown that phospholipid membranes induce a "molten" state of a water-soluble protein at binding.
2002. A book "Protein Physics" by A.V.Finkelstein & O.B.Ptitsyn has been published in Russian and in English (and in 2007 - in Chinese).
1999-2003. Theories of protein folding rates and folding nuclei are suggested, and algorithms searching for the folding nuclei and calculating folding rates from 3D structures of proteins us at the protein are developed.
1997-1999. A new approach has been elaborated to determine distances in a non-native state of a protein molecule using direct energy transfer of tryptophan fluorescence to modified tyrosines. Using this approach, a direct evidence for similarity of structural features of apomyoglobin in the molten globule and native states has been obtained.
1996-1998. It has been hypnotized that the folding nucleus consists of a set of evolutionary conserved non-functional amino acid residues, forming the highest number of contacts with the surrounding residues; an experimental testing of this hypothesis has been started.
1995-1997. It has been demonstrated that a fast folding pathway (with a low free energy of the transition state, i.e. of the nucleus) always leads to the lowest-energy fold. This solves the "Levinthal paradox". i.e., explains how the lowest-energy fold can be found within seconds rather than within the lifetime of the Universe.
1995. A hypothesis has been proposed that the molten globule state is involved in genetic diseases connected with point mutations in some proteins. These mutations can trap protein folding in the kinetic molten globule state.
1992-2004. It has been shown that chaperons GroEL/GroES do not accelerate protein folding; they rather, they make it slower, but more robust and less dependent on the environment of the folding chain. The large-scale motions in the GroEL/GroES system have been studied. A conventional model of covering of the folding protein chain by GroES has been refuted.
1992-2003. The folding-intermediate states other than the molten globule ("pre-molten globule", etc.) have been found and investigated.
1992-1999. The action of errors in energy estimates in protein structure prediction has been studied. It has been shown that common fold of remote homologs can be predicted correctly even when a correct prediction is impossible (due to errors in energy estimates) for all the individual chains.
1991-1995. The quasi-Boltzmann statistics of protein structures have been explained as a consequence of natural selection of stable folds of quasi-random sequences.
1988-2003. It has been proposed and experimentally demonstrated that the molten globule state is involved in some physiological process such as the transfer of hydrophobic ligands and interaction with chaperones. It has been shown that the molten globule state can be formed at mild denaturing conditions in the cell.
1988-1996. The first artificial protein with a new architecture and topology has been constructed and expressed in a cell-free system. The de novo design of this a b protein, albebetin, has been based on the theory of secondary and tertiary structures of a protein molecule. It has been shown that this de novo constructed protein has a stable compact molten globule structure. Albebetin has been modified to carry biological activity corresponding to that of interferon blast-transformation (1993-96), and later some other functions.
1987-1991. Investigation of globular protein folding kinetics has shown 3 states in protein folding: besides of conventional native and coil-like unfolded state, the molten globule-like kinetic intermediate has been discovered.
1985-1991. A general "threading" algorithm has been developed to calculate the free energy of protein fold and to choose the most appropriate folding pattern for a given sequence.
1982-1990. A theory has been elaborated for 3D-structures of random amino acid sequences. On the grounds of this theory a hypothesis has been proposed that globular proteins can be formed from quasi-random amino acid sequences. According to this hypothesis, the evolution of proteins is reduced to the "editing" of such sequences to give a necessary stability of 3D-structure and mainly to create an active center.
1982. A protein engineering technique has been proposed for the "grafting" of a desired active center to impart a new function.
1981-1989. The physical nature of protein denaturation has been studied and it has been shown that the first order phase transition upon protein denaturation is connected with the breakdown of the rigid tertiary structure rather than with general unfolding.
1981-1986. The molten globule state, a new physical state of the protein molecule, has been discovered and characterized in details.
1980-1987. A general theory has been developed for the packing of a-helices and b-strands into the compact globule. This theory forms a basis of rational classification of protein structure and reduces the problem of prediction of the protein folding pattern to the choice of the most appropriate folding pattern from their limited set.
1978. Abnormal kinetics of b-structure formation has been explained; the developed model can be also applied to the protein behavior in amyloid-like diseases.
1976-1984. A method has been elaborated for the study of large-scale molecular mobility in proteins by their diffuse X-ray scattering. It was shown that the functioning of some proteins (e.g. phosphoglycerate kinase) is accompanied by the locking and unlocking of their domains.
1974-1985. A molecular theory of protein secondary structure has been developed and the program package ALB (1982) has been elaborated for automatic prediction of protein and polypeptide secondary structure from their amino acid sequences.
1972-1973. A hypothesis has been proposed on the stepwise mechanism of protein 3D structure formation (now commonly called "the framework model").
1971-1974. A stereochemical theory of protein secondary structure has been developed.
1970. A phenomenological (statistical) theory of protein secondary structure has been developed.
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