References of "Konieczny, Leszek"
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See detailFuzzy oil drop model to interpret the structure of antifreeze proteins and their mutants
Banach, Mateusz; Prymula, Katarzyna; Jurkowski, Wiktor UL et al

in Journal of Molecular Modeling (2012), 18(1), 229-237

Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based ... [more ▼]

Mutations in proteins introduce structural changes and influence biological activity: the specific effects depend on the location of the mutation. The simple method proposed in the present paper is based on a two-step model of in silico protein folding. The structure of the first intermediate is assumed to be determined solely by backbone conformation. The structure of the second one is assumed to be determined by the presence of a hydrophobic center. The comparable structural analysis of the set of mutants is performed to identify the mutant-induced structural changes. The changes of the hydrophobic core organization measured by the divergence entropy allows quantitative comparison estimating the relative structural changes upon mutation. The set of antifreeze proteins, which appeared to represent the hydrophobic core structure accordant with "fuzzy oil drop" model was selected for analysis. [less ▲]

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See detailIntermediates in the protein folding process: a computational model
Roterman, Irena; Konieczny, Leszek; Banach, Mateusz et al

in International Journal of Molecular Sciences (2011), 12(8), 4850-60

The paper presents a model for simulating the protein folding process in silico. The two-step model (which consists of the early stage-ES and the late stage-LS) is verified using two proteins, one of ... [more ▼]

The paper presents a model for simulating the protein folding process in silico. The two-step model (which consists of the early stage-ES and the late stage-LS) is verified using two proteins, one of which is treated (according to experimental observations) as the early stage and the second as an example of the LS step. The early stage is based solely on backbone structural preferences, while the LS model takes into account the water environment, treated as an external hydrophobic force field and represented by a 3D Gauss function. The characteristics of 1ZTR (the ES intermediate, as compared with 1ENH, which is the LS intermediate) confirm the link between the gradual disappearance of ES characteristics in LS structural forms and the simultaneous emergence of LS properties in the 1ENH protein. Positive verification of ES and LS characteristics in these two proteins (1ZTR and 1ENH respectively) suggest potential applicability of the presented model to in silico protein folding simulations. [less ▲]

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See detailPrediction of functional sites based on the fuzzy oil drop model
Brylinski, Michal; Prymula, Katarzyna; Jurkowski, Wiktor UL et al

in PLoS Computational Biology (2007), 3(5), 1-2

A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of ... [more ▼]

A description of many biological processes requires knowledge of the 3-D structure of proteins and, in particular, the defined active site responsible for biological function. Many proteins, the genes of which have been identified as the result of human genome sequencing, and which were synthesized experimentally, await identification of their biological activity. Currently used methods do not always yield satisfactory results, and new algorithms need to be developed to recognize the localization of active sites in proteins. This paper describes a computational model that can be used to identify potential areas that are able to interact with other molecules (ligands, substrates, inhibitors, etc.). The model for active site recognition is based on the analysis of hydrophobicity distribution in protein molecules. It is shown, based on the analyses of proteins with known biological activity and of proteins of unknown function, that the region of significantly irregular hydrophobicity distribution in proteins appears to be function related. [less ▲]

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See detailThe indirect generation of long-distance structural changes in antibodies upon their binding to antigen
Piekarska, Barbara; Drozd, Anna; Konieczny, Leszek et al

in Chemical Biology & Drug Design (2006), 68(5), 276-83

An allosteric mechanism for the generation of long-distance structural alterations in Fab fragments of antibodies in immune complexes has been postulated and tested in theoretical and experimental ... [more ▼]

An allosteric mechanism for the generation of long-distance structural alterations in Fab fragments of antibodies in immune complexes has been postulated and tested in theoretical and experimental analysis. The flexing and/or torsion-derived forces exerted on the elbow region in Fab arms of bivalent antibodies upon binding to antigen were assumed to drive the disruption of hydrogen bonds which stabilize N- and C-terminal chain fragments in V-domains. This allows an extra movement in the elbow followed by a relaxation in the Fab arm and may generate long-distance effects if, in particular, the structural changes are generated asymmetrically involving one chain of the Fab arm only. This mechanism was studied by simulation of molecular dynamics. The local instability in the area involving the site of packing of the N-terminal chain fragment allows penetration and binding of the supramolecular dye Congo red that hence becomes an indicator of the initiated relaxation process and is also the prospective ligand in studies of designing drugs. The susceptibility to dye binding was observed in complexation of bivalent antibodies only, supplying the evidence that constraints associating the interaction with randomly distributed antigenic determinants drive the local structural changes in the V-domain followed by long-distance effects. [less ▲]

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See detailEarly-stage folding in proteins (in silico) sequence-to-structure relation
Brylinski, Michal; Konieczny, Leszek; Czerwonko, Patryk et al

in Journal of Biomedicine & Biotechnology (2005), 2005(2), 65-79

A sequence-to-structure library has been created based on the complete PDB database. The tetrapeptide was selected as a unit representing a well-defined structural motif. Seven structural forms were ... [more ▼]

A sequence-to-structure library has been created based on the complete PDB database. The tetrapeptide was selected as a unit representing a well-defined structural motif. Seven structural forms were introduced for structure classification. The early-stage folding conformations were used as the objects for structure analysis and classification. The degree of determinability was estimated for the sequence-to-structure and structure-to-sequence relations. Probability calculus and informational entropy were applied for quantitative estimation of the mutual relation between them. The structural motifs representing different forms of loops and bends were found to favor particular sequences in structure-to-sequence analysis. [less ▲]

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See detailConformational subspace in simulation of early-stage protein folding
Jurkowski, Wiktor UL; Brylinski, Michal; Konieczny, Leszek et al

in Proteins (2004), 55(1), 115-27

A probability calculus was used to simulate the early stages of protein folding in ab initio structure prediction. The probabilities of particular phi and psi angles for each of 20 amino acids as they ... [more ▼]

A probability calculus was used to simulate the early stages of protein folding in ab initio structure prediction. The probabilities of particular phi and psi angles for each of 20 amino acids as they occur in crystal forms of proteins were used to calculate the amount of information necessary for the occurrence of given phi and psi angles to be predicted. It was found that the amount of information needed to predict phi and psi angles with 5 degrees precision is much higher than the amount of information actually carried by individual amino acids in the polypeptide chain. To handle this problem, a limited conformational space for the preliminary search for optimal polypeptide structure is proposed based on a simplified geometrical model of the polypeptide chain and on the probability calculus. These two models, geometric and probabilistic, based on different sources, yield a common conclusion concerning how a limited conformational space can represent an early stage of polypeptide chain-folding simulation. The ribonuclease molecule was used to test the limited conformational space as a tool for modeling early-stage folding. [less ▲]

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