PubMed Health⌕ Search

Biomedical subjects

Badretdinov AYa

Publications and source records attributed to Badretdinov AYa.

5 recordsLinked to original sources
PubMed1998

How homologs can help to predict protein folds even though they cannot be predicted for individual sequences.

At present, one cannot predict the 3D structure of a protein directly from its sequence alone mainly because of errors in the energy estimates. However, a recently developed simple analytical theory (Finkelstein, 1998) shows that using a set of homologs (i.e., chains with numerous amino acid mutations but with equal 3D folds) one can average the interaction energies over the homologs and predict their common 3D fold even when predictions for individual sequences are wrong because the energy parameters are known only approximately. In this work we verify this theoretical conclusion by computer simulations performed with simplified models of protein chains.

Computer Simulation↗
PubMed1997

Rate of protein folding near the point of thermodynamic equilibrium between the coil and the most stable chain fold.

BACKGROUND: The problem of how a protein chain can find its most stable structure without exhaustive sorting of all its possible conformations is known as the 'Levinthal paradox'. The purpose of this paper is to elucidate this problem and to estimate the rate of folding to the most stable structure near the point of thermodynamic equilibrium between this structure and the coil. RESULTS: Folding is rapid when it occurs in the vicinity of a thermodynamic 'all-or-none' transition from the coil to the lowest-energy fold: here the misfolded and semifolded states cannot 'trap' the folding chain since, even taken together, all these states are less stable than both the initial coil and the final stable fold of the chain. A stable globular structure can be rapidly achieved via a 'nucleation-and-growth' folding pathway that provides a continuous entropy-by-energy compensation along the folding pathway and thus provides a low free energy of the transition state. CONCLUSIONS: At the point of transition of the coil to the lowest-energy fold, an N-residue chain folds normally in approximately exp(N2/3) ns. Therefore, a 100-residue chain finds its most stable fold within minutes rather than in 10(100) ps = 10(80) years, according to the famous paradoxical estimate of Levinthal.

Aprotinin↗
PubMed1995

Why do protein architectures have Boltzmann-like statistics?

A theoretical study has shown that the occurrence of various structural elements in stable folds of random copolymers is exponentially dependent on the own energy of the element. A similar occurrence-on-energy dependence is observed in globular proteins from the level of amino acid conformations to the level of overall architectures. Thus, the structural features stabilized by many random sequences are typical of globular proteins while the features rarely observed in proteins are those which are stabilized by only a minor part of the random sequences.

Computer Simulation↗
PubMed1993

Why are the same protein folds used to perform different functions?

A small number of folding patterns describe in outline most of the known protein globules, the same folds being found in non-homologous proteins with different functions. We show that the 'popular' folding patterns are those which, due to some thermodynamic advantages of their structure, can be stabilized by a lot of random sequences. In contrast, the folds which are rarely or never observed in natural globular proteins can be stabilized only by a tiny number of random sequences. The advantageous folds are few, they tolerate various primary structures, and therefore they can and ought to perform different functions. A connection between the inherent 'weak points' of protein folding patterns and positions of active sites are discussed.

Binding Sites↗