Biomedical subjects

Ulrich H E Hansmann

Publications and source records attributed to Ulrich H E Hansmann.

At least 19 recordsLinked to original sources

PubMed2007

Aggregation of beta-amyloid fragments.

The authors study the folding and aggregation of six chains of the beta-amyloid fragment 16-22 using Monte Carlo simulations. While the isolated fragment prefers a helical form at room temperature, in the system of six interacting fragments one observes both parallel and antiparallel beta sheets below a crossover temperature T(x) approximately equal to 420 K. The antiparallel sheets have lower energy and are therefore more stable. Above the nucleation temperature the aggregate quickly dissolves into widely separated, weakly interacting chains.

Amyloid beta-Peptides↗

PubMed2006

Computational assessment of the entropy of solvation of small-sized hydrophobic entities.

A high level polarizable force field is used to study the temperature dependence of hydrophobic hydration of small-sized molecules from computer simulations. Molecular dynamics (MD) simulations of liquid water at various temperatures form the basis of free energy perturbation calculations that consider the onset and growth of a repulsive sphere. This repulsive sphere acts as a model construct for the hydrophobic species. In the present study, an extension is pursued for seven independent target temperatures, ranging from close to the freezing point almost up to the boiling point of liquid water under standard conditions. Care is taken to maintain proper physico-chemical model descriptions by cross-checking with experimental water densities at the selected target temperatures. The polarizable force field description of molecular water turns out to be suitable throughout the entire temperature domain considered. Derivatives of the computed free energies of hydrophobic hydration with respect to the temperature give access to the changes in entropy. In practice the entropy differential is determined from the negative of the slope of tangential lines formed at a certain target temperature in the free energy profile. The obtained changes in entropy are negative for small-sized cavities, and hence reconfirm the basic ideas of the Lum-Chandler-Weeks theory on hydrophobic hydration of small-sized solutes.

Computer Simulation↗

PubMed2006

Side-chain and backbone ordering in a polypeptide.

We report results from multicanonical simulations of polyglutamic acid chains of length of ten residues. For this simple polypeptide we observe a decoupling of backbone and side-chain ordering in the folding process. While the details of the two transitions vary between the peptide in gas phase and in an implicit solvent, our results indicate that, independent of the specific surroundings, upon continuously lowering the temperature side-chain ordering occurs only after the backbone topology is completely formed.

Computer Simulation↗

PubMed2006

Support vector machines for prediction of dihedral angle regions.

MOTIVATION: Most secondary structure prediction programs target only alpha helix and beta sheet structures and summarize all other structures in the random coil pseudo class. However, such an assignment often ignores existing local ordering in so-called random coil regions. Signatures for such ordering are distinct dihedral angle pattern. For this reason, we propose as an alternative approach to predict directly dihedral regions for each residue as this leads to a higher amount of structural information. RESULTS: We propose a multi-step support vector machine (SVM) procedure, dihedral prediction (DHPRED), to predict the dihedral angle state of residues from sequence. Trained on 20,000 residues our approach leads to dihedral region predictions, that in regions without alpha helices or beta sheets is higher than those from secondary structure prediction programs. AVAILABILITY: DHPRED has been implemented as a web service, which academic researchers can access from our webpage http://www.fz-juelich.de/nic/cbb

Algorithms↗

PubMed2006

Folding of proteins with diverse folds.

Using parallel tempering simulations with high statistics, we investigate the folding and thermodynamic properties of three small proteins with distinct native folds: the all-helical 1RIJ, the all-sheet beta3s, and BBA5, which has a mixed helix-sheet fold. In all three cases, simulations with our energy function find the native structures as global minima in free energy at experimentally relevant temperatures. However, the folding process strongly differs for the three molecules, indicating that the folding mechanism is correlated with the form of the native structure.

Computer Simulation↗

PubMed2006

Optimized parallel tempering simulations of proteins.

We apply a recently developed adaptive algorithm that systematically improves the efficiency of parallel tempering or replica exchange methods in the numerical simulation of small proteins. Feedback iterations allow us to identify an optimal set of temperatures/replicas which are found to concentrate at the bottlenecks of the simulations. A measure of convergence for the equilibration of the parallel tempering algorithm is discussed. We test our algorithm by simulating the 36-residue villin headpiece subdomain HP-36 where we find a lowest-energy configuration with a root-mean-square deviation of less than 4 A to the experimentally determined structure.

Algorithms↗

PubMed2006

Short-time dynamics of the helix-coil transition in polypeptides.

We study the critical relaxation of the helix-coil transition in all-atom models of polyalanine chains. We show that at the critical temperature the decay of a completely helical conformation can be described by scaling relations that allow us estimating the pertinent critical exponents. The present approach opens a new way for characterizing transitions in proteins and may lead to a better understanding of their folding mechanism. An application of the technique to the 34-residue human parathyroid fragment PTH(1-34) supports universality of the helix-coil transition in homopolymers and (helical) proteins.

Computer Simulation↗

PubMed2005

Protein structure prediction by tempering spatial constraints.

The probability to predict correctly a protein structure can be enhanced through introduction of spatial constraints - either from NMR experiments or from homologous structures. However, the additional constraints lead often to new local energy minima and worse sampling efficiency in simulations. In this work, we present a new parallel tempering variant that alleviates the energy barriers resulting from spatial constraints and therefore yields to an enhanced sampling in structure prediction simulations.

Algorithms↗

PubMed2005

Efficient sampling of protein structures by model hopping.

We introduce a novel simulation method, model hopping, that enhances sampling of low-energy configurations in complex systems. The approach is illustrated for a protein-folding problem. Thermodynamic quantities of proteins with up to 46 residues are evaluated from all-atom simulations with this method.

Algorithms↗

PubMed2005

Energy landscape paving simulations of the trp-cage protein.

We evaluate the efficiency of multiple variants of energy landscape paving in all-atom simulations of the trp-cage protein using a recently developed new force field. Especially, we introduce a temperature-free variant of the method and demonstrate that it allows a fast scanning of the energy landscape. Nativelike structures are found in less time than by other techniques. The sampled low-energy configurations indicate a funnel-like energy landscape.

Journal Article↗

PubMed2005

Exploring protein energy landscapes with hierarchical clustering.

In this work we present a new method for investigating local energy minima on a protein energy landscape. The CABS (CAlpha, CBeta and the center of mass of the Side chain) method was employed for generating protein models, but any other method could be used instead. Cα traces from an ensemble of models are hierarchical clustered with the HCPM (Hierarchical Clustering of Protein Models) method. The efficiency of this method for sampling and analyzing energy landscapes is shown.

Journal Article↗

PubMed2004

Simulations of a small protein in a specifically designed generalized ensemble.

We describe a variant of the generalized-ensemble approach that allows faster simulations for special classes of proteins. We test this technique for an all-atom model of the 36-residue protein HP-36. The dependence of various thermodynamic quantities on small modifications of the solvent representation is explored. Configurations with a root-mean square deviation of less than 4 A to the experimentally determined structure are observed.

Algorithms↗

PubMed2004

Generalized-ensemble simulations of the human parathyroid hormone fragment PTH(1-34).

A generalized-ensemble technique, multicanonical sampling, is used to study the folding of a 34-residue human parathyroid hormone fragment. An all-atom model of the peptide is employed and the protein-solvent interactions are approximated by an implicit solvent. Our results demonstrate that generalized-ensemble simulations are well suited to sample low-energy structures of such large polypeptides. Configurations with a root-mean-square deviation to the crystal structure of less than 1 A are found. Finally, we discuss limitations of our implicit solvent model.

Humans↗

PubMed2004

All-atom generalized-ensemble simulations of small proteins.

We give an overview of some generalized-ensemble techniques that have proven successful in all-atom simulations of proteins. We show that these techniques enable efficient investigations of secondary structure formation and folding in peptides and small proteins. Results are presented for various alanine-based artificial peptides and a small protein, the 36-residued villin headpiece subdomain (HP-36). Our results indicate that all-atom simulations of proteins may be more restricted by the accuracy of the present energy functions than by the efficiency of the search algorithms.

Computer Simulation↗

PubMed2003

Helix versus sheet formation in a small peptide.

Segments with the amino acid sequence EKAYLRT (glutamine-lysine-alanine-tyrosine-leucine-arginine-threonine) appear in naturally occurring proteins both in alpha-helices and beta-sheets. For this reason, we have used this peptide to study how secondary structure formation in proteins depends on the local environment. Our data rely on multicanonical Monte Carlo simulations where the interactions among all atoms are taken into account. Results in gas phase are compared with that in an implicit solvent. We find that both the solvated molecule and EKAYLRT in gas phase form an alpha-helix when not interacting with other molecules. However, in the vicinity of a beta-strand, the peptide forms a beta-strand. Because of this change in secondary structure our peptide may provide a simple model for the alpha-->beta transition that is supposedly related to the outbreak of prion diseases and similar illnesses.

Amino Acid Sequence↗

PubMed2003

Parallel tempering simulations of HP-36.

We report results from all-atom Monte Carlo simulations of the 36-residue villin headpiece subdomain HP-36. Protein-solvent interactions are approximated by an implicit solvent model. The parallel tempering is used to overcome the problem of slow convergence in low-temperature protein simulations. Our results show that this technique allows one to sample native-like structures of small proteins and points out the need for improved energy functions.

Algorithms↗

PubMed2002

Energy landscape paving for X-ray structure determination of organic molecules.

The efficiency of a recently proposed novel global optimization method, energy landscape paving (ELP), is evaluated with regard to the problem of crystal structure determination from simulated X-ray diffraction data comprising integrated diffraction intensities. The new approach has been tested using the example of 9-(methylamino)-1H-phenalen-1-one 1,4-dioxan-2-y1 hydroperoxide solvate (C14H11NO.C4H8O4). The results indicate that, for this example, ELP outperforms standard techniques such as simulated annealing.

Journal Article↗

PubMed2002

Numerical comparison of two approaches for the study of phase transitions in small systems.

We compare two recently proposed methods for the characterization of phase transitions in small systems. The validity and usefulness of these approaches are studied for the cases of the q=4 and q=5 Potts model, i.e., systems where a thermodynamic limit and exact results exist. Guided by this analysis we then discuss the helix-coil transition in polyalanine, an example of structural transitions in biological molecules.

Journal Article↗