Free energy self-averaging in protein-sized random heteropolymers

Current theories of heteropolymers are inherently macroscopic, but are applied to mesoscopic proteins. To compute the free energy over sequences, one assumes self-averaging--a property established only in the macroscopic limit. By enumerating the states and energies of compact 18, 27, and 36mers on a lattice with an ensemble of random sequences, we test the self-averaging approximation. We find that fluctuations in the free energy between sequences are weak, and that self-averaging is valid at the scale of real proteins. The results validate sequence design methods which exponentially speed up computational design and simplify experimental realizations.     

Multicanonical chain-growth algorithm

We present a temperature-independent Monte Carlo method for the determination of the density of states of lattice proteins that combines the fast ground-state search strategy of the new pruned-enriched Rosenbluth chain-growth method and multicanonical reweighting for sampling the complete energy space. Since the density of states contains all energetic information of a statistical system, we can directly calculate the mean energy, specific heat, Helmholtz free energy, and entropy for all temperatures. We apply this method to lattice proteins consisting of hydrophobic and polar monomers, and for the examples of sequences considered, we identify the transitions between native, globule, and random coil states. Since no special properties of heteropolymers are involved in this algorithm, the method applies to polymer models as well.     

Spectral properties of contact matrix: Application to proteins

A protein can be modelled by a set of points representing its amino acids. Topologically, this set of points is entirely defined by its contact matrix (adjacency matrix in graph theory). The contact matrix characterizing the relation between neighboring amino acids is deduced from Voronoi or Laguerre decomposition. This method allows contact matrices to be defined without any arbitrary cut-off that could induce arbitrary effects. Eigenvalues of these matrices are related with elementary excitations in proteins. We present some spectral properties of these matrices that reflect global properties of proteins. The eigenvectors indicate participation of each amino acids to the excitation modes of the proteins. It is interesting to compare the protein modelled as a close packing of amino acids, with a random close packing of spheres. The main features of the protein are those of a packing, a result that confirms the importance of the dense packing model for proteins. Nevertheless there are some properties, specific to the hierarchical organization of the protein: the primary chain order, the secondary structures and the domain structures.     

Structurally constrained protein evolution: results from a lattice simulation

We simulate the evolution of a protein-like sequence subject to point mutations, imposing conservation of the ground state, thermodynamic stability and fast folding. Our model is aimed at describing neutral evolution of natural proteins. We use a cubic lattice model of the protein structure and test the neutrality conditions by extensive Monte Carlo simulations. We observe that sequence space is traversed by neutral networks, i.e. sets of sequences with the same fold connected by point mutations. Typical pairs of sequences on a neutral network are nearly as different as randomly chosen sequences. The fraction of neutral neighbors has strong sequence to sequence variations, which influence the rate of neutral evolution. In this paper we study the thermodynamic stability of different protein sequences. We relate the high variability of the fraction of neutral mutations to the complex energy landscape within a neutral network, arguing that valleys in this landscape are associated to high values of the neutral mutation rate. We find that when a point mutation produces a sequence with a new ground state, this is likely to have a low stability. Thus we tentatively conjecture that neutral networks of different structures are typically well separated in sequence space. This result indicates that changing significantly a protein structure through a biologically acceptable chain of point mutations is a rare, although possible, event. Received 8 July 1999     

Theoretical and computational study of high-pressure structures in barium

Recent high-pressure work has suggested that elemental barium forms a high-pressure self-hosting structure (Ba IV) involving two "types" of barium atom. Uniquely among reported elemental structures it cannot be described by a single crystalline lattice, instead involving two interpenetrating incommensurate lattices. In this Letter we report pseudopotential calculations demonstrating the stability and the potentially disordered nature of the "guest" structure. Using band structures and nearly free electron theory we relate the appearance of Ba IV to an instability in the close-packed structure, demonstrate that it has a zero energy vibrational mode, and speculate about the structure's stability in other divalent elements.     

An elastic-plastic contact model for line contact structures

Although numerical simulation tools are now very powerful,the development of analytical models is very important for the prediction of the mechanical behaviour of line contact structures for deeply understanding contact problems and engineering applications.For the line contact structures widely used in the engineering field,few analytical models are available for predicting the mechanical behaviour when the structures deform plastically,as the classic Hertz’s theory would be invalid.Thus,the present study proposed an elastic-plastic model for line contact structures based on the understanding of the yield mechanism.A mathematical expression describing the global relationship between load history and contact width evolution of line contact structures was obtained.The proposed model was verified through an actual line contact test and a corresponding numerical simulation.The results confirmed that this model can be used to accurately predict the elastic-plastic mechanical behaviour of a line contact structure.     

Designing protein beta-sheet surfaces by Z-score optimization

Studies of lattice models of proteins have suggested that the appropriate energy expression for protein design may include nonthermodynamic terms to accommodate negative design concerns. One method, developed in lattice model studies, maximizes a quantity known as the " Z-score," which compares the lowest energy sequence whose ground state structure is the target structure to an ensemble of random sequences. Here we show that, in certain circumstances, the technique can be applied to real proteins. The resulting energy expression is used to design the beta-sheet surfaces of two real proteins. We find experimentally that the designed proteins are stable and well folded, and in one case is even more thermostable than the wild type.     

Microscopic spectrum of the Wilson Dirac operator

We calculate the leading contribution to the spectral density of the Wilson Dirac operator using chiral perturbation theory where volume and lattice spacing corrections are given by universal scaling functions. We find analytical expressions for the spectral density on the scale of the average level spacing, and introduce a chiral random matrix theory that reproduces these results. Our work opens up a novel approach to the infinite-volume limit of lattice gauge theory at finite lattice spacing and new ways to extract coefficients of Wilson chiral perturbation theory.     

Folding/unfolding kinetics of lattice proteins studied using a simple statistical mechanical model for protein folding, I: Dependence on native structures and amino acid sequences

The folding/unfolding kinetics of a three-dimensional lattice protein was studied using a simple statistical mechanical model for protein folding that we developed earlier. We calculated a characteristic relaxation rate for the free energy profile starting from a completely unfolded structure (or native structure) that is assumed to be associated with a folding rate (or an unfolding rate). The chevron plot of these rates as a function of the inverse temperature was obtained for four lattice proteins, namely, proteins a1, a2, b1, and b2, in order to investigate the dependency of the folding and unfolding rates on their native structures and amino acid sequences. Proteins a1 and a2 fold to the same native conformation, but their amino acid sequences differ. The same is the case for proteins b1 and b2, but their native conformation is different from that of proteins a1 and a2. However, the chevron plots of proteins a1 and a2 are very similar to each other, and those of proteins b1 and b2 differ considerably. Since the contact orders of proteins b1 and b2 are identical, the differences in their kinetics should be attributed to the amino acid sequences and consequently to the interactions between the amino acid residues. A detailed analysis revealed that long-range interactions play an important role in causing the difference in the folding rates. The chevron plots for the four proteins exhibit a chevron rollover under both strongly folding and strongly unfolding conditions. The slower relaxation time on the broad and flat free energy surfaces of the unfolding conformations is considered to be the main origin of the chevron rollover, although the free energy surfaces have features that are rather complicated to be described in detail here. Finally, in order to concretely examine the relationship between changes in the free energy profiles and the chevron plots, we illustrate some examples of single amino acid substitutions that increase the folding rate.     

Systematics of collective correlation energies from self-consistent mean-field calculations

We study nucleon-nucleon scattering on the lattice at next-to-leading order in chiral effective field theory. We determine phase shifts and mixing angles from the properties of two-nucleon standing waves induced by a hard spherical wall in the center-of-mass frame. At fixed lattice spacing we test model independence of the low-energy effective theory by computing next-to-leading-order corrections for two different leading-order lattice actions. The first leading-order action includes instantaneous one-pion exchange and same-site contact interactions. The second leading-order action includes instantaneous one-pion exchange and Gaussian-smeared interactions. We find that in each case the results at next-to-leading order are accurate up to corrections expected at higher order.     

Overlap distribution in random and designed heteropolymers

We study the overlap between low-energy states in lattice models of heteropolymers with contact interactions. The overlap distribution gives information on the degree of correlation in the energy landscape. Designed sequences have rather correlated energy landscapes, which favor fast folding kinetics. Chains with random interactions have much less correlated energy landscapes. It is indeed believed that the mean-field theory for this model coincides with the Random Energy Model, whose different low-energy states are completely unrelated. This picture has been supported by numerical studies of maximally compact configurations. Without applying this constraint, we find that the overlap distribution is indeed bimodal as expected, but it has a broad peak at large overlap, indicating a non-vanishing width for the valleys of low-energy states. This feature probably plays an important role in the kinetics of the model. It is not evident that the range of such correlations shrinks to zero for large systems. The range of the correlations seems to be influenced by the number of contacts per residue in the ground state: the smaller this quantity, the larger the correlations. Received 16 August 2000     

Micro/macro-slip damping in beams with frictional contact interface

Friction in contact interfaces of assembled structures is the prime source of nonlinearity and energy dissipation. Determination of the dissipated energy in an assembled structure requires accurate modeling of joint interfaces in stick, micro-slip and macro-slip states. The present paper proposes an analytical model to evaluate frictional energy loss in surface-to-surface contacts. The goal is to develop a continuous contact model capable of predicting the dynamics of friction interface and dissipation energy due to partial slips. To achieve this goal, the governing equations of a frictional contact interface are derived for two distinct contact states of stick and partial slip. A solution procedure to determine stick–slip transition under single-harmonic excitations is derived. The analytical model is verified using experimental vibration test responses performed on a free-frictionally supported beam under lateral loading. The theoretical and experimental responses are compared and the results show good agreements between the two sets of responses.     

Glasslike structure of globular proteins and the boson peak

Vibrational spectra of proteins and topologically disordered solids display a common anomaly at low frequencies, known as boson peak. We show that such feature in globular proteins can be deciphered in terms of an energy landscape picture, as it is for glassy systems. Exploiting the tools of Euclidean random matrix theory, we clarify the physical origin of such anomaly in terms of a mechanical instability of the system. As a natural explanation, we argue that such instability is relevant for proteins in order for their molecular functions to be optimally rooted in their structures.     

Exact solution for temerature field due to non-equilibrium heating of solid substrate

Non-equilibrium energy transfer between electron and lattice sub-systems due to short-pulse heating is formulated and the closed form solution for electron and lattice site temperatures is presented. The electron kinetic theory approach is incorporated to formulate non-equilibrium energy transfer in the electron and lattice sub-systems. The method of Lie point symmetries is used in the exact solution of governing energy equation. In the analysis, the volumetric heat source, representing the laser heating pulse, and surface heat source, corresponding to short thermal contact of the surface, are incorporated and the analytical solutions for each heating source are presented. Electron temperature distribution obtained from the closed form solution is compared with its counterpart predicted from the numerical simulation. It is found that the results obtained from the closed form agree well with electron temperature predictions obtained from numerical simulation.     

Asymptotics of the partition function of a general Markov random field on an infinite rectangular lattice

We investigate theoretically and numerically the asymptotics of the partition function of a general Markov random field (MRF) on an infinite rectangular lattice. We first propose the general local energy function (LEF)-parameterized MRF. Then we prove that the thermodynamic limit of the free energy of the MRF can be exactly characterized by the Perron root of the fundamental transfer matrix of a particular Markov additive process (MAP). This matrix possesses a special structure and many interesting properties that enable parallel computation of the Perron root and may be beneficial for deriving an analytical form of the free energy. We also develop another transfer matrix for numerical computation of the desired Perron root. Specifically, the former is a site-to-site transfer matrix on a twisted cylindrical lattice, while the latter is the one associated with a row-to-row transition on a vertical strip. Numerical results show that our methods exhibit consistent finite-size scaling behavior even for small values of the lattice width. This study reveals that the fundamental transfer matrix is an alternative direction of research on the analysis of the partition function of general MRFs within the scope of matrix algebra.     

Dimers and the Critical Ising Model on lattices of genus >1

We study the partition function of both Close-Packed Dimers and the Critical Ising Model on a square lattice embedded on a genus two surface. Using numerical and analytical methods we show that the determinants of the Kasteleyn adjacency matrices have a dependence on the boundary conditions that, for large lattice size, can be expressed in terms of genus two theta functions. The period matrix characterizing the continuum limit of the lattice is computed using a discrete holomorphic structure. These results relate in a direct way the lattice combinatorics with conformal field theory, providing new insight to the lattice regularization of conformal field theories on higher genus Riemann surfaces.     

Lattice QCD with overlap fermions on GPUs

Lattice QCD is widely considered the correct theory of the strong force and is able to make quantitative statements in the low energy regime where perturbation theory is not applicable. The partition function of lattice QCD can be mapped onto a statistical mechanics system which then allows for the use of calculational methods such as Monte Carlo simulations. In recent years, the enormous success of GPU programming has also arrived at the lattice community. In this article, we give a short overview of Lattice QCD and motivate this need for large computing power. In our simulations we concentrate on a specific fermionic discretization, so-called Neuberger-Dirac fermions, which respect an exact chiral symmetry. We will discuss the algorithms we use in our GPU implementation which turns out to be an order of magnitude faster then the conventional CPU-equivalent. As an application we present results on the eigenvalue spectra in QCD and compare them to analytical calculations from Random Matrix Theory.     

点阵平面几何学

本文用欧几里得算法,给出求解基矢变换对应矩阵的解析表达式。分析了点阵平面及复合点阵平面的画法,并指出其应用范围。 关键词：     

Eigenvalue density of the non-Hermitian Wilson Dirac operator

We find the lattice spacing dependence of the eigenvalue density of the non-Hermitian Wilson Dirac operator in the ? domain. The starting point is the joint probability density of the corresponding random matrix theory. In addition to the density of the complex eigenvalues we also obtain the density of the real eigenvalues separately for positive and negative chiralities as well as an explicit analytical expression for the number of additional real modes.