Krzysztof Nowiński

Quantum-Dynamical Picture of a Multistep Enzymatic Process: Reaction Catalyzed by Phospholipase A 2

A quantum-classical molecular dynamics model (QCMD), applying explicit integration of the time-dependent Schrödinger equation (QD) and Newtonian equations of motion (MD), is presented. The model is capable of describing quantum dynamical processes in complex biomolecular systems. It has been applied in simulations of a multistep catalytic process carried out by phospholipase A(2) in its active site. The process includes quantum-dynamical proton transfer from a water molecule to histidine localized in the active site, followed by a nucleophilic attack of the resulting OH(-) group on a carbonyl carbon atom of a phospholipid substrate, leading to cleavage of an adjacent ester bond. The process has been simulated using a parallel version of the QCMD code. The potential energy function for the active site is computed using an approximate valence bond (AVB) method. The dynamics of the key proton is described either by QD or classical MD. The coupling between the quantum proton and the classical atoms is accomplished via Hellmann-Feynman forces, as well as the time dependence of the potential energy function in the Schrödinger equation (QCMD/AVB model). Analysis of the simulation results with an Advanced Visualization System revealed a correlated rather than a stepwise picture of the enzymatic process. It is shown that an sp(2)--> sp(3) configurational change at the substrate carbonyl carbon is mostly responsible for triggering the activation process.

Molecular mechanics calculations of molecular and chiral recognition by cyclodextrins. Is it reliable? The selective complexation of decalins by β-cyclodextrin

Abstract Molecular mechanics calculations are frequently used to rationalize experimental findings concerning molecular and chiral recognition by cyclodextrins although the reliability of the method in general and the influence of choice of the parameters in particular has not almost been analyzed. In this work molecular and chiral recognition of decalin isomers by β-cyclodextrin was studied using amber , cvff , cff91 , and mmx force fields and five values of dielectric constant ϵ =1, 2, 4, 10, 20. Most calculations yielded consistently lower stability of the complex with trans -decalin. However, in most cases the absolute value of the energy difference between the stabilization energies of the complexes with the latter isomer and the one with cis -decalin closer to it, |ΔΔ E molec |, characterizing molecular recognition was found smaller than the corresponding value involving cis -decalin enantiomers, |ΔΔ E chir |=|Δ E M - cis −Δ E P - cis |, characterizing chiral recognition. The calculations indicate no preference for complexation with either M - cis or P - cis decalin enantiomer. Therefore, we believe that MM is not suitable for reliable analysis of chiral recognition by cyclodextrins. Although the ϵ value of 1 was found unreliable for molecular mechanics calculations using all FF under study, our preliminary results of molecular dynamics calculations in water for the complexes of camphor and pinene enantiomers with α-cyclodextrin using the latter value yielded qualitatively correct results.

Structure of cyclodextrins and their complexes: Part 2. Do cyclodextrins have a rigid truncated-cone structure?2

Abstract Model molecular mechanics calculations using the MM2 force field reveal high complexity of the energy hypersurface of α-cyclodextrin. In spite of limited accuracy of the calculations carried out under many simplifying assumptions, the results obtained seem to indicate that the isolated molecule is highly flexible. This conclusion seems to be valid for cyclodextrin solutions but the flexibility of the host is expected to be restricted in complexes. Such a qualitative conclusion is in agreement with NMR studies of cyclodextrins and their complexes with aromatic guests on the one hand and with their ability to form complexes with guest molecules of various shapes on the other.

‘Horror vacui’ or topological in-out isomerism in perhydrogenated fullerenes: C60H60 and monoalkylated perhydrogenated fullerenes☆

Abstract In endohedral chemistry, one of the exciting prospects offered by the cage-like structure of fullerenes, several aspects of the calculations on in-out isomerism of perhydrogenated fullerene and their consequences went unnoticed, e.g. the topological character of the isomerism, the instability of C 60 F 60 , which was thought to revolutionize industry as an ideal lubricant, as well as the possibility of in-out isomerism in alkylated fulleranes. Molecular mechanics calculations indicate that for smaller alkyl groups the ‘in’ isomer is significantly more stable extending the possibility of endohedral fullerene chemistry. C 60 H 60 and its derivatives can be considered as examples of a manifestation of the ancient ‘horror vacui’ concept.

Determining Geometrically Stable Domains in Molecular Conformation Sets.

Detecting significant conformational changes occurring in biomolecules is a challenging task, especially when considering tens to hundreds of thousands of conformations. Conformational variability can be described by dividing a biomolecule into dynamic domains, i.e., by finding compact fragments that move as coherent units. Typical approaches, based on calculating a dynamical cross-correlation matrix, are limited by their inability to reveal correlated rotations and anticorrelated motions. We propose a geometric approach for finding dynamic domains, where we compare traces of atomic movements in a pairwise manner, and search for their best superposition. A quaternion representation of rotation is used to simplify the complex calculations. The algorithm was implemented in a Java graphical program: Geometrically Stable Substructures (GeoStaS). The program processes PDB and DCD binary files with large structural sets for proteins, nucleic acids, and their complexes. We demonstrate its efficiency in analyzing (a) ensembles of structures generated by NMR experiments and (b) conformation sets from biomolecular simulations, such as molecular dynamics. The results provide a clear description of the molecular movements even for large biomolecules. Compared to a standard dynamic cross-correlation matrix, our algorithm detects the correlations in both translational and rotational motions.

TOPOLOGICAL ISOMERISM : SHOULD ROTAXANES, ENDOHEDRAL FULLERENE COMPLEXES AND IN-OUT ISOMERS OF HYDROGENATED FULLERENES BE CONSIDERED AS SUCH ?

Abstract Rotaxanes are not considered to be topological isomers of their separated fragments. However, due to their similarity to catenanes, they are often discussed within the realm of topological chemistry. Similarly, “in” fullerene isomers (endohedral complexes, nested fullerenes, and the isomers of hydrogenated fullerenes) have not, until recently, been treated as topological isomers of the corresponding “out” isomers. In this paper the problem of topological isomerism is analysed departing from the standard topological notions of arbitrary continuous deformations imposed on the system under investigation as a sufficient condition for topological isomerism. Similarly to the isomer classification into conformational and configurational isomers, the energy barrier between the trivial (e. g., separated rings) and non-trivial (e. g., catenated) topological structures should be invoked into such classifications to limit allowed deformations of the systems under investigation. A precise mathematical model of the classification, based on topological invariants, is presented in an Appendix. Contrary to commonly accepted definitions, the problem of topological isomerism is analysed departing from the notions of arbitrary continuous deformations imposed on the system as a sufficient condition for the isomerism. The energy barrier between the trivial (e. g., separated fragments) and non-trivial (e. g., catenated) topological structures is invoked to limit allowed deformations and include the titles molecules into the realm of topological chemistry.

On the impossibility of determination of stepwise binding constants for the 1 ∶ 2 complex of (+)-camphor with α-cyclodextrin

Knowledge of stepwise binding constants for complexes with higher than 1:1 stoichiometry would allow one to study the cooperativity of their formation. However, a detailed analysis of partitioning of the overall binding constant beta 12 determined by NMR titrations for the 1:2 complex of (+)-camphor with alpha-cyclodextrin into the stepwise ones K1 and K2 carried out analogously to published procedures revealed that the partitioning cannot be carried out unequivocally for K1 << K2. The programs for partitioning cannot be used as a black box and a satisfactory reproduction of the experimental dependence of relative shifts as a function of relative CD concentration should not be the only criterion of the reliability of the stepwise binding constants obtained using such programs.

Generation of dynamic heart model based on 4d echocardiographic images

One of the most challenging problems in the modern cardiology is a correct quantification of the left ventricle contractility and synchronicity. Correct, quantitative assessment of these parameters, which could be changed in a course of many severe diseases of the heart (e.g. coronary artery disease and myocardial infarction, heart failure), is a key factor for the right diagnose and further therapy. Up to date, in clinical daily practice, most of these information is collected by transthoracic two dimensional echocardiography. Assessment of these parameters is difficult and depends on observer experience. However, quantification method of the contractility assessment based on strain and strain analysis are available, these methods still are grounded on 2D analysis. Real time 3D echocardiography gives physicians opportunity for real quantitative analysis of the left ventricle contractility and synchronicity. In this work we present a method for estimating heart motion from 4D (3D+time) echocardiographic images.

Unigrids streaming framework: enabling streaming for the new generation of grids

We present a new infrastructure for high performance streaming in OGSA/WSRF compliant grid. The UniGrids Streaming Framework (UGSF) works with UnicoreGS as WSRF hosting environment. The paper discusses the advantages of mixed SOAP based control with highly efficient streaming. The UGSF components, streaming server and WSRF web service are described along with a detailed performance analysis including comparison to standard solutions. Some applications based on the UGSF are also presented.

The quest for a planar and pyramidal carbon atom Part 4: An unsuccessful search for pyramidal carbon atoms in hypothetical unsaturated conjugated paddlane

Abstract Ab initio HF and DFT calculations indicate that tetraeneoctayn 8 cannot assume structure 8a of D4th symmetry with two pyramidal carbon atoms. Instead, it assumes the minimum structure 8b , characterized by unusual angular distortions of CCC fragments.