arXiv subjects

Ulrich H. E. Hansmann

Publications and source records attributed to Ulrich H. E. Hansmann.

At least 19 recordsLinked to original sources

arXiv2021

Resolution Exchange with Tunneling for Enhanced Sampling of Protein Landscapes

Simulations of protein folding and protein association happen on timescales that are orders of magnitude larger than what can typically be covered in all-atom molecular dynamics simulations. Use of low-resolution models alleviates this problem but may reduce the accuracy of the simulations. We introduce a replica-exchange-based multiscale sampling technique that combines the faster sampling in coarse-grained simulations with the potentially higher accuracy of all-atom simulations. After testing the efficiency of our Resolution Exchange with Tunneling (ResET) in simulations of the Trp-cage protein, an often used model to evaluate sampling techniques in protein simulations, we use our approach to compare the landscape of wild type and A2T mutant Abeta 1-42 peptides. Our results suggest a mechanism by that the mutation of a small hydrophobic Alanine (A) into a bulky polar Threonine (T) may interfere with the self-assembly of Abeta - fibrils.

physics.comp-ph↗

arXiv2019

Pearl-Necklace-Like Local Ordering Drives Polypeptide Collapse

Collapse of the polypeptide backbone is an integral part of protein folding. Using polyglycine as a probe, we explore the nonequilibrium pathways of protein collapse in water. We find that the collapse depends on the competition between hydration effects and intra-peptide interactions. Once intra-peptide van der Waal interactions dominate, the chain collapses along a nonequilibrium pathway characterized by formation of pearl-necklace-like local clusters as intermediates that eventually coagulate into a single globule. By describing this coarsening through the contact probability as a function of distance along the chain, we extract a time-dependent length scale that grows in linear fashion. The collapse dynamics is characterized by a dynamical critical exponent $z=0.5$ that is much smaller than the values of $z=1-2$ reported for non-biological polymers. This difference in the exponents is explained by the instantaneous formation of intra-chain hydrogen bonds and local ordering that may be correlated with the observed fast folding times in proteins.

physics.bio-ph↗

arXiv2007

Dispersion Terms and Analysis of Size- Charge Dependence in an Enhanced Poisson Boltzmann Approach

We implement a well-established concept to consider dispersion effects within a Poisson-Boltzmann approach of continuum solvation of proteins. The theoretical framework is particularly suited for boundary element methods. Free parameters are determined by comparison to experimental data as well as high-level quantum mechanical reference calculations. The method is general and can be easily extended in several directions. The model is tested on various chemical substances and found to yield good-quality estimates of the solvation free energy without obvious indication of any introduced bias. Once optimized, the model is applied to a series of proteins, and factors such as protein size or partial charge assignments are studied.

physics.bio-ph↗

arXiv2007

Optimizing Replica Exchange Moves For Molecular Dynamics

In this short note we sketch the statistical physics framework of the replica exchange technique when applied to molecular dynamics simulations. In particular, we draw attention to generalized move sets that allow a variety of optimizations as well as new applications of the method.

q-bio.QM↗

arXiv2007

On Dynamics and Optimal Number of Replicas in Parallel Tempering Simulations

We study the dynamics of parallel tempering simulations, also known as the replica exchange technique, which has become the method of choice for simulation of proteins and other complex systems. Recent results for the optimal choice of the control parameter discretization allow a treatment independent of the system in question. Analyzing mean first passage times across control parameter space, we find an expression for the optimal number of replicas in simulations covering a given temperature range. Our results suggest a particular protocol to optimize the number of replicas in actual simulations.

cond-mat.stat-mech↗

arXiv2007

Generalized Ensemble and Tempering Simulations: A Unified View

From the underlying Master equations we derive one-dimensional stochastic processes that describe generalized ensemble simulations as well as tempering (simulated and parallel) simulations. The representations obtained are either in the form of a one-dimensional Fokker-Planck equation or a hopping process on a one-dimensional chain. In particular, we discuss the conditions under which these representations are valid approximate Markovian descriptions of the random walk in order parameter or control parameter space. They allow a unified discussion of the stationary distribution on, as well as of the stationary flow across each space. We demonstrate that optimizing the flow is equivalent to minimizing the first passage time for crossing the space, and discuss the consequences of our results for optimizing simulations. Finally, we point out the limitations of these representations under conditions of broken ergodicity.

cond-mat.stat-mech↗

arXiv2007

Short-time dynamics of polypeptides

The authors study the short-time dynamics of helix-forming polypeptide chains using an all-atom representation of the molecules and an implicit solvation model to approximate the interaction with the surrounding solvent. The results confirm earlier observations that the helix-coil transition in proteins can be described by a set of critical exponents. The high statistics of the simulations allows the authors to determine the exponents values with increased precision and support universality of the helix-coil transition in homopolymers and (helical) proteins.

q-bio.OT↗

arXiv2006

Side-chain and backbone ordering in Homopolymers

In order to study the relation between backbone and side chain ordering in proteins, we have performed multicanonical simulations of deka-peptide chains with various side groups. Glu10, Gln10, Asp10, Asn10, and Lys10 were selected to cover a wide variety of possible interactions between the side chains of the monomers. All homopolymers undergo helix-coil transitions. We found that peptides with long side chains that are capable of hydrogen bonding, i.e. Glu10, and Gln10, exhibit a second transition at lower temperatures connected with side chain ordering. This occurs in gas phase as well as in solvent, although the character of the side chain structure is different in each case. However, in polymers with short side chains capable of hydrogen bonding, i.e. Asp10 and Asn10, side chain ordering takes place over a wide temperature range and exhibits no phase transition like character. Moreover, non-backbone hydrogen bonds show enhanced formation and fluctuations already at the helix-coil transition temperature, indicating competition between side chain and backbone hydrogen bond formation. Again, these results are qualitatively independent of the environment. Side chain ordering in Lys10, whose side groups are long and polar, also takes place over a wide temperature range and exhibits no phase transition like character in both environments. Reasons for the observed chain length threshold and consequences from these results for protein folding are discussed.

cond-mat.stat-mech↗

arXiv2006

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 sub-domain HP-36 wherewe find a lowest-energy configuration with a root-mean-square-deviation of less than 4 Angstroem to the experimentally determined structure.

q-bio.QM↗

arXiv2003

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 (rmsd) to the crystal structure of less than one Åare found. Finally, we discuss limitations of our implicit solvent model.

cond-mat.stat-mech↗

arXiv2003

Helix vs. Sheet Formation in a Small Peptide

Segments with the amino acid sequence EKAYLRT appear in natural occurring proteins both in $α$-helices and $β$-sheets. For this reason, we have use 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 in gas phase and solvated EKAYLRT forms an $α$-helix when not interacting with other molecules. However, in the vicinity of a $β$-strand, the peptide forms a $β$-strand. Because of this change in secondary structure our peptide may provide a simple model for the $α\to β$ transition that is supposedly related to the outbreak of Prion diseases and similar illnesses.

cond-mat.soft↗

arXiv2002

Solution effects and the order of the helix-coil transition in polyalanine

We study helix-coil transitions in an all-atom model of polyalanine. Molecules of up to length 30 residues are investigated by multicanonical simulations. Results from two implicit solvent models are compared with each other and with that from simulations in gas phase. While the helix-coil transition is in all three models a true thermodynamic phase transition, we find that its strength is reduced by the protein-solvent interaction term. The order of the helix-coil transition depends on the details of the solvation term.

cond-mat.stat-mech↗

arXiv2002

Helix Formation and Folding in an Artificial Peptide

We study the relation between $α$-helix formation and folding for a simple artificial peptide, Ala$_{10}$-Gly$_5$-Ala$_{10}$. Our data rely on multicanonical Monte Carlo simulations where the interactions among all atoms are taken into account. The free-energy landscape of the peptide is evaluated for various temperatures. Our data indicate that folding of this peptide is a two-step process: in a first step two $α$-helices are formed which afterwards re-arrange themselves into a U-like structure.

cond-mat.stat-mech↗

arXiv2001

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 case 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 discuss then the helix-coil transition in polyalanine, an example of structural transitions in biological molecules.

cond-mat.stat-mech↗

arXiv2001

Proteinlike behavior of a spin system near the transition between ferromagnet and spin glass

A simple spin system is studied as an analog for proteins. We investigate how the introduction of randomness and frustration into the system effects the designability and stability of ground state configurations. We observe that the spin system exhibits protein-like behavior in the vicinity of the transition between ferromagnet and spin glass. Our results illuminate some guiding principles in protein evolution.

cond-mat.stat-mech↗

arXiv2001

Thermodynamics and Kinetics of Folding of a Small Peptide

We study the thermodynamics and kinetics of folding for a small peptide. Our data rely on Monte Carlo simulations where the interactions among all atoms are taken into account. Monte Carlo kinetics is used to study folding of the peptide at suitable temperatures. The results of these canonical simulations are compared with that of a generalized-ensemble simulation. Our work demonstrates that concepts of folding which were developed in the past for minimalist models hold also for this peptide when simulated with an all-atom force field.

cond-mat↗

arXiv2000

Yang-Lee zeros and the helix-coil transition in a continuum model of polyalanine

We calculate the Yang-Lee zeros for characteristic temperatures of the helix-coil transition in a continuum model of polyalanine. The distribution of these zeros differs from predictions of the Zimm-Bragg theory and supports recent claims that polyalanine exhibits a true phase transition. New estimates for critical exponents are presented and the relation of our results to the Lee-Yang theorem is discussed.

cond-mat.stat-mech↗

arXiv2000

Partition function zeros and leading order scaling correction of the 3D Ising model from multicanonical simulations

The density of states for the three-dimensional Ising model is calculated with high-precision from multicanonical simulations. This allows us to estimate the leading partition function zeros for lattice sizes up to L=32. Combining previous statistics for smaller lattice sizes, we have evaluated the correction to scaling and the critical exponent $ν$ through out an analysis of a multi-parameter fit and of Bulirsch-Stoer (BST) extrapolation algorithm. The performance of the BST algorithm is also explored in case of the 2D Ising model, where the exact partition function zeros are known.

cond-mat.stat-mech↗