Andrzej Rabczenko

Protein-protein recognition: Method of finding complementary surfaces of interacting proteins

A new method is described for searching for complementary surfaces of protein molecules from known coordinates of their non-hydrogen atoms. Each atom is assigned an arbitrary feature which is specific of its interactions with other atoms. The plots representing surfaces are generated. For each pair of surfaces a number of coincidences is calculated which increases as the number of contacts is increased between these atom pairs whose contribution to the energy of interaction is considered to be essential. The results obtained for the well-known autoassociation of insulin show the applicability of the method for the prediction of possible reaction modes between macromolecules.

Methods of molecular modelling of protein-protein interactions

This article reviews briefly theoretical methods attempting to predict the structure of protein aggregates from the structural features of their subunits. The authors discuss the problems of the solvent effect and the formation of protein structure. The existing methods of quaternary structure prediction are presented and an attempt at their classification is made at the end of this review.

Searching for interacting surfaces of proteins--the improved method.

Protein-protein recognition involves matching of pairs of surfaces endowed with specific properties which provide for so many attractive interactions that the possibility of any competitive combination is ruled out and stability of the resulting aggregate is secured. It is, then, topology of the two surfaces that is essential, and also the nature of intereacting groups. Several methods on analysis of protein-protein interactions have already been described (Levinthal et al., 1975; Feldman et al., 1978; Greer & Bush, 1978; Wodak & Janin, 1978; Morgan, Miller & McAldon, 1979; Salemme, 1979; Wistow et al., 1981 ; Milner-White, 1982). We have recently suggested a simple, efficient method for searching for complementary surfaces of interacting proteins (Zielenkiewicz & Rabczenko, 1984). Here we report the improved version of this method. In our previous paper (Zielenkiewicz & Rabczenko, 1984) we presented the method for searching for complementary surfaces based on planar projections of surface atoms. Atoms were arbitrarily assigned certain features, e.g. hydrophobicity and hydrophilicity. The projection plane was scaled by a network of squares. A layer of atoms was projected onto a plane so that the van der Waals sphere of an atom containing the co-ordinates of a centre of a network square caused the square to be attributed the feature characteristic of this atom. The part of the network comprising the entire area of projection was then described by a matrix, named projection matrix A. We then searched for the pair of matrices for which the number of coincident elements (what was called the number of coincidences--NOC) was the greatest. The main drawbacks of the method were: (i) the three-dimensional surface topology was lost in the process of projection and (ii) there was no method for identification of surface atoms, i.e. all the atoms from the layer of given thickness were projected. The improvements presented below overcome the drawbacks mentioned. 6O7

Pseudorotation of the ribofuranose ring. A theoretical study and a comparison with nuclear magnetic resonance results

The results of energy calculations by means of the consistent force field method performed for methyl β-D-ribofuranoside are presented. Two regions of stable pentose conformations are predicted, other than those observed for the ribose moiety in most nucleosides. Local energy minima are associated with different conformations of the hydroxy and hydroxymethylene groups. Models of the molecule in solution are proposed, for which proton coupling constants are calculated; a satisfactory agreement with experimental 1H n.m.r. coupling constants is achieved. The influence of the exocyclic substituents and of the orientation of the hydroxy groups on the conformation of the furanose ring and on its interconversion by pseudorotation is discussed.

Simulation of the interconversion path between stable conformations of the furanose ring: methyl β-D-2-deoxyribofuranoside and simpler ribose and deoxyribose analogues

The results of simulation of the pseudorotation path in methyl β-D-2-deoxyribofuranoside, cyclopentane, tetrahydrofuran, 3-hydroxytetrahydrofuran, and 2,3-dihydroxytetrahydrofuran by using a geometrical ring-puckering model and an empirical all-atom force-field method are presented. For all these molecules energetic and geometric profiles of the N–S interconversion pathway are presented for various exocyclic group orientations. The difference in the simulated conformational behaviour of certain model compounds in the vapour state and in polar-solution conditions is discussed. The influence of the orientation and presence of exocyclic groups and the role of C- and O-ring structure on the conformational behaviour of the compounds examined is investigated. Conformational analysis of the furanose ring in several model compounds of increasing structure complexity reveals great diversity in their conformational behaviour in both geometric and energetic respects. The only features of conformational behaviour attributed to ring structure are: (a) the existence of energy minima in wide N and S regions of pseudorotation wheel; (b) the existence of N–S interconversion path via puckered-ring conformations. The puckering amplitude q varies considerably during N–S interconversion path and is no longer a quantitative feature of furanosering structure.

Conformational analysis of the deoxyribofuranose ring: a theoretical study

The results of energy calculations by the Consistent Force Field method for methyl β-D-2-deoxyribofuranoside are presented. Two regions of stable pentose conformations are predicted; within each region local energy minima are associated with different conformations of the hydroxy and hydroxymethylene groups. A conformational model of the molecule in solution is proposed. Proton coupling constants are calculated for the stable conformers found, and a qualitative agreement with the experimentally observed solution behaviour is achieved. The influence of the nature and conformation of exocyclic substituents on the conformation of the furanose ring and on the interconversion of conformations by pseudorotation is discussed.

Calculation of average values for CC bond lengths and CCC bond angles. PCILO conformational study of n-butane with the newly found and other molecular geometries

Abstract The best average values for CC bond lengths and CCC bond angles were calculated for fragments in which the CC bond was at least one CC bond distant from heavy atom substituents by using the results of searches of the Cambridge Structural Database. The values found, 1.51 A and 113° for a CCCH3 fragment, and 1.52 A and 114° for a fragment inside a carbon chain, differ significantly from the values commonly used in theoretical calculations which are generally based on a limited set of crystallographic data or on the diamond structure. To test the sensitivity of quantum-chemical energy calculation methods to different input geometries, the PCILO method was taken as an example and checked for reproducibility of experimental conformational energy for the n-butane molecule. Energy minimization with respect to the CC bond length and the CCC bond angle led to values of 1.49 A and 115°, respectively. For this geometry the gauche conformation was found to be preferred by 1.4 kJ mol−1 over the trans conformation. This result is inconsistent with experimental data and indicates that the proper choice of geometrical parametrization is of the greatest importance in energy calculations.

Conformation of nucleosides. Dipole moments of pyrimidine nucleosides.

Abstract The dipole moments of a series of model pyrimidine nucleosides were determined experimentally. Comparison was made between the experimental values and those vectorially calculated as a function of nucleoside conformation. This analysis alone does not permit the unequivocal determination of the conformation of the nucleoside in solution, but taken together with the circular dichroism data from the adjoining paper (Rabczenko, A., Jankowski, K. and Zakrzewska, K. (1974) Biochim. Biophys. Acta) suggests: (i) the possibility of the existence of isopropylidene derivatives in dioxane in a mixture of syn and anti conformers; (ii) the conformational equilibrium of the N ag S type for a model nucleoside with a non-rigid sugar moiety.

A new description of equilateral five-membered rings during pseudorotation

An equilateral, five-membered ring is described based on the assumption that during conformational changes the distances between atoms and the position of the centre of mass of the ring remain constant. In the course of pseudorotation the atoms move along three-dimensional curves whose projections on a mean plane of the ring are circles. Assuming a certain bond length of the initial regular pentagon, the model allows for high accuracy calculations of the geometry of any future conformations of the ring. Our model is compared with those of Kilpatrick and Adams.

A general geometrical model for pseudorotation simulation in five-membered rings

A geometrical model for simulation of pseudorotation in five-membered rings, based on the assumption hat during pseudorotational changes the bond lengths and position of geometrical centre of the ring remain constant, is presented. The significance of the ‘planar reference conformation’ is discussed and the method of calculation of this conformation from the knowledge of the ring bond lengths is described. The ‘planar reference conformations’ of cyclopentane, tetrahydrofuran, and 1,3-dioxolane molecules calculated in this way are in a fair agreement with the corresponding ab initio results. The geometries of 183 β-D-furanoside fragments are reconstructed in the frame of our model and also those of Kilpatrick et al., Adams et al., and Altona and his co-workers. The results obtained within our model are the closest to the crystallographic ones. A special version of our model, parametrized for the furanose ring, is also presented.