Biomedical subjects

Hannes H Loeffler

Publications and source records attributed to Hannes H Loeffler.

5 recordsLinked to original sources

PubMed2006

Water exchange dynamics of lithium(I) ion in aqueous solution.

The water exchange dynamics of the fourfold coordinated first hydration shell of the lithium(I) ion was studied by both direct and umbrella sampling QM/MM-MD and classical MD simulations. The structural changes and energetics accompanying the activation process are discussed. The overall exchange rate constant was found to be k(ex) = 5.8 x 10(9) s(-1) from classical MD simulations. QM/MM-MD umbrella sampling simulations predict an exchange rate constant of k(TST) = 1.01 x 10(10) s(-1) as obtained from classical transition-state theory. First-shell ligands exchange preferably via an associatively activated mode.

Cations↗

PubMed2003

Many-body effects on structure and dynamics of aqueous ionic solutions.

We performed several molecular dynamic studies of metal cations in aqueous solution. The alkali metal ion Li(+) and the first-row transition metal ion Mn(2+) have been chosen as model systems. Two different three-body corrections are proposed to mimic the crucial many-body effects of electrolyte solutions. The correction function, which includes attractive features of the three-body potential, performs considerably better than the purely repulsive interaction function. Structural and dynamic results show that this simple enhancement is able to satisfactorily reproduce experimental and higher-level results for the first hydration shell.

Journal Article↗

PubMed2003

A QM-MM interface between CHARMM and TURBOMOLE: implementation and application to systems in bulk phase and biologically active systems.

The implementation of a hybrid QM-MM approach combining ab initio and density functional methods of TURBOMOLE with the molecular mechanics program package CHARMM is described. An interface has been created to allow data exchange between the two applications. With this method the efficient multiprocessor capabilities of TURBOMOLE can be utilized with CHARMM running as a single processor application. Therefore, features of nonparallel running code in CHARMM like the TRAVEL module for locating saddle points or VIBRAN for the calculation of second derivatives can be exploited by running the CPU intensive QM calculations in parallel. To test the methodology, several small systems are studied with both Hartree-Fock and density functional methods and varying QM-MM boundaries. Also, the computationally efficient RI-J method has been examined for use in QM-MM applications. A B(12) cofactor containing cobalt has been studied, to examine systems with a large QM region and transition metals. All tested methods perform satisfactory in comparison with pure quantum calculations. Additionally, algorithms for the characterization of saddle points have been tested for their potential use in QM-MM problems. The TRAVEL module of CHARMM has been applied to the Menshutkin reaction in the condensed phase, and a saddle point was located. This saddle point was verified by calculation of a steepest descent path connecting educt, transition state, and product, and by calculation of vibrational modes.

Cobamides↗

PubMed2003

Influence of backbone conformations of human carbonic anhydrase II on carbon dioxide hydration: hydration pathways and binding of bicarbonate.

In this study, the hydration of carbon dioxide and the formation of bicarbonate in human carbonic anhydrase II have been examined. From semiempirical QM/MM molecular dynamics studies, dominant conformations of the protein backbone, possibly contributing to the catalytic activity, have been isolated and further examined by means of density functional QM/MM methods. In agreement with experimental observations, a binding site for cyanate, which acts as an inhibitor, has been located, whereas for carbon dioxide, depending on the conformation of the protein environment, either a different binding site or no binding site has been found. In the latter case, carbon dioxide diffuses barrierless to the zinc-bound oxygen, and then a weakly bound bicarbonate complex is formed. The formed complex is characterized by a long C-O bond to the zinc-bound hydroxide. The nature of the calculated stationary points was verified by determination of vibrational frequencies. Finally, the dissociation of the formed bicarbonate from zinc has been considered. Therefore, a water molecule was included in the QM zone of the QM/MM hybrid potential, and minimization yielded a pentacoordinated intermediate. From a potential energy scan, an activation energy of 6.2 kcal/mol for dissociation of bicarbonate from Zn has been found.

Bicarbonates↗

PubMed2003

Structure and dynamics of metal ions in solution: QM/MM molecular dynamics simulations of Mn(2+) and V(2+).

Structural and dynamical properties of the transition metal ions V(2+) and Mn(2+) in aqueous solution, resulting from combined quantum mechanical (QM)/molecular mechanical (MM) molecular dynamics (MD) simulations have been compared. The necessity of polarization functions on the ligand's oxygen for a satisfactory description of such ions in aqueous solution is shown using V(2+) as test case. Radial distribution functions, coordination number distributions, and several angle distributions were pursued for a detailed structural comparison of the first hydration shells. Dynamical properties, such as the librational and vibrational motions of water molecules were evaluated by means of velocity autocorrelation functions. Approximative normal coordinate analyses were employed to calculate the rotational frequencies and vibrational motions around the three principal axes. The very low exchange rates for the first shell water exchanges only allow an investigation of the water exchange processes in the second shell, which take place within the picosecond range.

Cations, Divalent↗