Wolfgang Damm - Academia.edu (original) (raw)

Papers by Wolfgang Damm

ChemInform

The diastereofacial selectivity in reactions of a series of alkyl-substituted cyclohexyl radicals... more The diastereofacial selectivity in reactions of a series of alkyl-substituted cyclohexyl radicals has been investigated. In additions of cyclohexyl radicals to alkenes, it has been found that only substituents bound at the olefinic center being attacked by the radical influence the equatorial-axial selectivity. Substituents bound to the radical center or axial substituents-beta to the radical center lead to increased axial attack. Equatorial beta-substituents or axial gamma-substituents increase the amount of equatorial attack. The same trends are observed for halogen and hydrogen abstraction reactions; the amount of axial reaction product is usually somewhat higher than in the addition reactions. The stereoselectivities can be explained with steric and torsional effects very similar to those suggested for nucleophilic addition reactions to cyclohexanones. A MM2 force field has been parameterized to gain further insight into the stereochemistry of the reaction.

Journal of Computational Chemistry

... 404K). Keywords: carbohydrates; hexopyranoses; conformational analysis; ab initio;force field... more ... 404K). Keywords: carbohydrates; hexopyranoses; conformational analysis; ab initio;force field. Abstract. The OPLS all-atom (AA) force field for organic and biomolecular systems has been expanded to include carbohydrates. ...

Journal of Materials Chemistry, 2002

This paper introduces a probabilistic extension of UML statecharts. A requirements-level semantic... more This paper introduces a probabilistic extension of UML statecharts. A requirements-level semantics of statecharts is extended to include probabilistic elements. Desired properties for probabilistic statecharts are expressed in the probabilistic logic PCTL, and verified using the model checker Prism. The extension simplifies the verification of critical systems with probabilistic elements, e. g. fault-tolerant systems. The extension is illustrated using a

The Journal of Physical Chemistry B, 2004

ABSTRACT The conformational preferences about the glycosidic linkages present in β-laminarabiose ... more ABSTRACT The conformational preferences about the glycosidic linkages present in β-laminarabiose and β-gentiobiose in water are investigated by comparing molecular dynamics (MD) simulations with results from NMR spectroscopy (coupling constants, NOE-derived distances), X-ray crystallography (structures), and molecular mechanics (adiabatic energy maps). The simulations are performed using the OPLS−AA−SEI force field recently developed for hexopyranoses and extended to account for the properties of the linkages present in the two disaccharides. The experimental and theoretical results for β-laminarabiose are very consistent and reveal a clear correlation between the conformation around the dihedral angle ψ and the presence of an interresidue hydrogen bond (from the 4-hydroxyl group of the reducing residue to the ring oxygen of the nonreducing residue). The solvent (water) plays an essential role in determining the preferential orientation about ψ, by dramatically reducing the strength of this intramolecular hydrogen bond. Application of the OPLS−AA−SEI force field to β-gentiobiose requires significant adjustments of the torsional parameters and electrostatic scaling scheme. After optimization of the force field based on ab initio calculations in a vacuum and on the experimental population profile around the dihedral angle ω in water, the OPLS−AA−SEI force field is able to give a realistic representation of the conformational behavior of the β(1→6) linkage on the nanosecond time scale. As expected, the glycosidic dihedral angles in this linkage present an enhanced flexibility compared to the β(1→3) linkage. The results of the two simulations point (in line with previous studies) toward the need of developing a new Karplus-type equation relating hetero-nuclear 3JC,H coupling constants to the glycosidic dihedral angle φ. They also suggest that the Karplus-type equation of Stenutz et al. for the homo-nuclear 3JH,H coupling constant is superior to the widely used equation of Haasnoot et al.

Tetrahedron Letters, 1991

... 1952, 74, 5828. 2. NA Porter, B. Giese, DP Curran, Acc.Chem.Res. in press. 3. O.Strouf, J. Fu... more ... 1952, 74, 5828. 2. NA Porter, B. Giese, DP Curran, Acc.Chem.Res. in press. 3. O.Strouf, J. Fusek, O. Cervinka, COll.CZech.Chem.COmmun. 1974, 39, 1044; R. PerezOssorio, C. Alvarez Ibarra, ML Quiroga, MS AriasPerez, MJ FemandezDominguez, E. Moya Molina, Ann.Chim. ...

Tetrahedron Letters, 1996

... 4 A Astrain 4 B FelkinAnh 0 kcal mol 3.0 kcal mol 353 Meg 2.36 A i " 95 2" 8A 8B Bu... more ... 4 A Astrain 4 B FelkinAnh 0 kcal mol 3.0 kcal mol 353 Meg 2.36 A i " 95 2" 8A 8B But 0.0 kcal mol Bu' H CN H.. Me CN Me 0.3 kcal mol But I Me 9A HCN 9B "CN But 8.6 keal mol Bu' H CN 229 ,PCN But 0.0 ... AM1 calculations: MJS Dewar, EG Zoebisch, EF Healy, JJ Stewart, J. Am ...

Journal of the American Chemical Society, 1993

... 1991, 24, 139. (2) (a) Giese, B. Angew. Chem., Int. Ed. Engl. 1989,28,969. (b) Damm, W.;Giese... more ... 1991, 24, 139. (2) (a) Giese, B. Angew. Chem., Int. Ed. Engl. 1989,28,969. (b) Damm, W.;Giese,B.;Hartung, J.;Hasskerl,T.;Houk,KN;Zipse,H. J.Am. Chem. Soc. 1992. 114. 4067. (3) For' review, see: Porter, N. A.; Giese, B.; Curran, DP Acc. Chem. Res. 1991. 24. 296. -,- , ...

Journal of the American Chemical Society, 1992

Journal of Computational Chemistry, 2002

This work describes an improved version of the original OPLS-all atom (OPLS-AA) force field for c... more This work describes an improved version of the original OPLS-all atom (OPLS-AA) force field for carbohydrates (Damm et al., J Comp Chem 1997, 18, 1955). The improvement is achieved by applying additional scaling factors for the electrostatic interactions between 1,5- and 1,6-interactions. This new model is tested first for improving the conformational energetics of 1,2-ethanediol, the smallest polyol. With a 1,5-scaling factor of 1.25 the force field calculated relative energies are in excellent agreement with the ab initio-derived data. Applying the new 1,5-scaling makes it also necessary to use a 1,6-scaling factor for the interactions between the C4 and C6 atoms in hexopyranoses. After torsional parameter fitting, this improves the conformational energetics in comparison to the OPLS-AA force field. The set of hexopyranoses included in the torsional parameter derivation consists of the two anomers of D-glucose, D-mannose, and D-galactose, as well as of the methyl-pyranosides of D-glucose, D-mannose. Rotational profiles for the rotation of the exocyclic group and of different hydroxyl groups are also compared for the two force fields and at the ab initio level of theory. The new force field reduces the overly high barriers calculated using the OPLS-AA force field. This leads to better sampling, which was shown to produce more realistic conformational behavior for hexopyranoses in liquid simulation. From 10-ns molecular dynamics (MD) simulations of alpha-D-glucose and alpha-D-galactose the ratios for the three different conformations of the hydroxymethylene group and the average (3)J(H,H) coupling constants are derived and compared to experimental values. The results obtained for OPLS-AA-SEI force field are in good agreement with experiment whereas the properties derived for the OPLS-AA force field suffer from sampling problems. The undertaken investigations show that the newly derived OPLS-AA-SEI force field will allow simulating larger carbohydrates or polysaccharides with improved sampling of the hydroxyl groups.

Journal of Computational Chemistry, 2000

ABSTRACT Temperature-dependent nuclear magnetic resonance (NMR) and CD spectra of methanol soluti... more ABSTRACT Temperature-dependent nuclear magnetic resonance (NMR) and CD spectra of methanol solutions of a β-heptapeptide have been interpreted in such a way that the secondary structure, a 314-helix, is assumed to be stable in a temperature range of between 298 and 393 K. This is in contrast to the results of a 50-ns molecular dynamics simulation using the GROMOS96 force field, which found a melting temperature of about 340 K. This discrepancy is addressed by further computational studies using the OPLS-AA force field. The conformational energetics of N-formyl-3-aminobutanamide in vacuo are obtained using ab initio and density functional quantum-mechanical calculations at the HF/6-31G*, B3LYP/6-31G*, and B3LYP/6-311+G* levels of theory. The results permit development of torsional parameters for the OPLS-AA force field that reproduce the conformational energetics of the monomer. By varying the development procedure, three parameter sets are obtained that focus on reproducing either low-energy or high-energy conformations. These parameter sets are tested by simulating the reversible folding of the β-heptapeptide in methanol. The melting temperature of the helix formed (>360 K) is found to be higher than the one obtained from simulations using the GROMOS96 force field (∼340 K). Differences in the potential energy functions of the latter two force fields are evaluated and point to the origins of the difference in stability. © 2000 John Wiley & Sons, Inc. J Comput Chem 21: 774–787, 2000

Journal of Computational Chemistry, 1997

Journal of Computational Chemistry, 2005

We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent devel... more We provide an overview of the IMPACT molecular mechanics program with an emphasis on recent developments and a description of its current functionality. With respect to core molecular mechanics technologies we include a status report for the fixed charge and polarizable force fields that can be used with the program and illustrate how the force fields, when used together with new atom typing and parameter assignment modules, have greatly expanded the coverage of organic compounds and medicinally relevant ligands. As we discuss in this review, explicit solvent simulations have been used to guide our design of implicit solvent models based on the generalized Born framework and a novel nonpolar estimator that have recently been incorporated into the program. With IMPACT it is possible to use several different advanced conformational sampling algorithms based on combining features of molecular dynamics and Monte Carlo simulations. The program includes two specialized molecular mechanics modules: Glide, a high-throughput docking program, and QSite, a mixed quantum mechanics/molecular mechanics module. These modules employ the IMPACT infrastructure as a starting point for the construction of the protein model and assignment of molecular mechanics parameters, but have then been developed to meet specialized objectives with respect to sampling and the energy function.

Journal of Chemical Theory and Computation, 2005

A polarizable force field, and associated continuum solvation model, have been developed for the ... more A polarizable force field, and associated continuum solvation model, have been developed for the explicit purpose of computing and studying the energetics and structural features of protein binding to the wide range of ligands with potential for medicinal applications. Parameters for the polarizable force field (PFF) are derived from gas-phase ab initio calculations and then utilized for applications in which the protein binding to ligands occurs in aqueous solvents, wherein the charge distributions of proteins and ligands can be dramatically altered. The continuum solvation model is based on a self-consistent reaction field description of solvation, incorporating an analytical gradient, that allows energy minimizations (and, potentially, molecular dynamics simulations) of protein/ligand systems in continuum solvent. This technology includes a nonpolar model describing the cost of cavity formation, and van der Waals interactions, between the continuum solvent and protein/ligand solutes. Tests of the structural accuracy and computational stability of the methodology, and timings for energy minimizations of proteins and protein/ligand systems in the condensed phase, are reported. In addition, the derivation of polarizability, electrostatic, exchange repulsion, and torsion parameters from ab initio data is described, along with the use of experimental solvation energies for determining parameters for the solvation model.

Journal of Chemical Theory and Computation, 2010

The accurate prediction of protein−ligand binding free energies is a primary objective in compute... more The accurate prediction of protein−ligand binding free energies is a primary objective in computer-aided drug design. The solvation free energy of a small molecule provides a surrogate to the desolvation of the ligand in the thermodynamic process of protein−ligand binding. ...

Biophysical Journal, 2007

Schizophyllan is a b(1/3)-D-glucan polysaccharide with b(1/6)-branched lateral glucose residues t... more Schizophyllan is a b(1/3)-D-glucan polysaccharide with b(1/6)-branched lateral glucose residues that presents a very stiff triple-helical structure under most experimental conditions. Despite the remarkable stability of this structure (which persists up to 120°C in aqueous solution), schizophyllan undergoes a major change of state around 7°C in water that has been hypothesized to result from an order-disorder transition in the lateral residues. This hypothesis is only supported by indirect experimental evidence and detailed knowledge (at the atomic level) concerning hydrogen-bonding networks, interactions with the solvent molecules, orientational freedom of the lateral residues, and orientational correlations among them is still lacking. In this study explicit-solvent molecular dynamics simulations of a schizophyllan fragment (complemented by simulations of its tetrasaccharide monomer) are performed at three different temperatures (273 K, 350 K, and 450 K) and with two different types of boundary conditions (finite nonperiodic or infinite periodic fragment) as an attempt to provide detailed structural and dynamical information about the triple-helical conformation in solution and the mechanism of the low-temperature transition. These simulations suggest that three important driving forces for the high stability of the triple helix are i), the limited conformational work involved in its formation; ii), the formation of a dense hydrogen-bonding network at its center; and iii), the formation of interchain hydrogen bonds between main-chain and lateral glucose residues. However, these simulations evidence a moderate and continuous variation of the simulated observables upon increasing the temperature, rather than a sharp transition between the two lowest temperatures (that could be associated with the state transition). Although water-mediated hydrogen-bonded association of neighboring lateral residues is observed, this interaction is not strong enough to promote the formation of an ordered state (correlated motions of the lateral residues), even at the lowest temperature considered.

Tetrahedron, 2000

AbstractÐIn order to understand the heterolytic cleavage of 4 H -DNA radical 1 and the regioselec... more AbstractÐIn order to understand the heterolytic cleavage of 4 H -DNA radical 1 and the regioselective attack of nucleophiles at the intermediate DNA radical cation 3, the chemistry of model radical 8 was studied. It turned out that the heterolytic cleavage in water is favored over homolysis because of the effective solvation of the ions 9 and 10. The regioselectivity of the nucleophilic attack at radical cation 10 can be explained with the valence bond con®guration mixing (VBCM) model. q Scheme 1. General overview of the reaction pathways of C4 H -DNA radical and of its model system 8.