arXiv subjects

Marek Cieplak

Publications and source records attributed to Marek Cieplak.

At least 55 records · Page 3Linked to original sources

arXiv2005

Stretching of proteins in a force-clamp

Mechanically induced protein unfolding in the force-clamp apparatus is shown, in a coarse-grained model of ubiquitin, to have lognormal statistics above a treshold force and exponential below it. Correspondingly, the mean unfolding time is slowly varying and exponentially decreases as a function of the force. The time dependencies of the end-to-end distances are also distinct. The time sequence of unfolding events weakly depends on force and much of it resembles that for stretching at constant speed. A more complicated time dependence arises for integrin.

q-bio.BM↗

arXiv2004

Mechanical Stretching of Proteins: Calmodulin and Titin

Mechanical unfolding of several domains of calmodulin and titin is studied using a Go-like model with a realistic contact map and Lennard-Jones contact interactions. It is shown that this simple model captures the experimentally observed difference between the two proteins: titin is a spring that is tough and strong whereas calmodulin acts like a weak spring with featureless force-displacement curves. The difference is related to the dominance of the alpha secondary structures in the native structure of calmodulin. The tandem arrangements of calmodulin unwind simultaneously in each domain whereas the domains in titin unravel in a serial fashion. The sequences of contact events during unraveling are correlated with the contact order, i.e. with the separation between contact making amino acids along the backbone in the native state. Temperature is found to affect stretching in a profound way.

q-bio.BM↗

arXiv2004

Chirality and Protein Folding

There are several simple criteria of folding to a native state in model proteins. One of them involves crossing of a threshold value of the RMSD distance away from the native state. Another checks whether all native contacts are established, i.e. whether the interacting amino acids come closer than some characteristic distance. We use Go-like models of proteins and show that such simple criteria may prompt one to declare folding even though fragments of the resulting conformations have a wrong sense of chirality. We propose that a better condition of folding should augment the simple criteria with the requirement that most of the local values of the chirality should be nearly native. The kinetic discrepancy between the simple and compound criteria can be substantially reduced in the Go-like models by providing the Hamiltonian with a term which favors native values of the local chirality. We study the effects of this term as a function of its amplitude and compare it to other models such as with the side groups and with the angle-dependent potentials.

q-bio.BM↗

arXiv2004

Mechanical properties of the domains of titin in a Go-like model

Comparison of properties of three domains of titin, I1, I27 and I28, in a simple geometry-based model shows that despite a high structural homology between their native states different domains show similar but distinguishable mechanical properties. Folding properties of the separate domains are predicted to be diversified which reflects sensitivity of the kinetics to the details of native structures. The Go-like model corresponding to the experimentally resolved native structure of the I1 domain is found to provide the biggest thermodynamic and mechanical stability compared to the other domains studied here. We analyze elastic, thermodynamic and kinetic properties of several structures corresponding to the I28 domain as obtained through homology-based modeling. We discuss the ability of the models of the I28 domain to reproduce experimental results qualitatively. A strengthening of contacts that involve hydrophobic amino acids does not affect theoretical comparisons of the domains. Tandem linkages of up to five identical or different domains unravel in a serial fashion at low temperatures. We study the nature of the intermediate state that arises in the early stages of the serial unraveling and find it to qualitatively agree with the results of Marszalek et al.

q-bio.BM↗

arXiv2004

Lattice tube model of proteins

We present a new lattice model for proteins that incorporates a tube-like anisotropy by introducing a preference for mutually parallel alignments in the conformations. The model is demonstrated to capture many aspects of real proteins.

q-bio.BM↗

arXiv2004

What one can learn from experiments about the elusive transition state?

We present the results of an exact analysis of a model energy landscape of a protein to clarify the notion of the transition state and the physical meaning of the $ϕ$ values determined in protein engineering experiments. We benchmark our findings to various theoretical approaches proposed in the literature for the identification and characterization of the transition state.

q-bio.BM↗

arXiv2004

Cooperativity and Contact Order in Protein Folding

The effects of cooperativity are studied within Go-Lennard-Jones models of proteins by making the contact interactions dependent on the proximity to the native conformation. The kinetic universality classes are found to remain the same as in the absence of cooperativity. For a fixed native geometry, small changes in the effective contact map may affect the folding times in a chance way and to the extent that is comparable to the shift in the folding times due to cooperativity. The contact order controlls folding scenarios: the average times necessary to bring pairs of amino acids into their near native separations depend on the sequential distances within the pairs. This dependence is largely monotonic, regardless of the cooperativity, and the dominant trend could be described by a single parameter like the average contact order. However, it is the deviations from the trend which are usually found to set the net folding times.

q-bio.BM↗

arXiv2003

Thermal effects in stretching of Go-like models of titin and secondary structures

The effect of temperature on mechanical unfolding of proteins is studied using a Go-like model with a realistic contact map and Lennard-Jones contact interactions. The behavior of the I27 domain of titin and its serial repeats is contrasted to that of simple secondary structures. In all cases thermal fluctuations accelerate the unraveling process, decreasing the unfolding force nearly linearly at low temperatures. However differences in bonding geometry lead to different sensitivity to temperature and different changes in the unfolding pattern. Due to its special native state geometry titin is much more thermally and elastically stable than the secondary structures. At low temperatures serial repeats of titin show a parallel unfolding of all domains to an intermediate state, followed by serial unfolding of the domains. At high temperatures all domains unfold simultaneously and the unfolding distance decreases monotonically with the contact order, that is the sequence distance between the amino acids that form the native contact.

q-bio.BM↗

arXiv2003

Stretching of Proteins in the Entropic Limit

Mechanical stretching of six proteins is studied through molecular dynamics simulations. The model is Go-like, with Lennard-Jones interactions at native contacts. Low temperature unfolding scenarios are remarkably complex and sensitive to small structural changes. Thermal fluctuations reduce the peak forces and the number of metastable states during unfolding. The unfolding pathways also simplify as temperature rises. In the entropic limit, all proteins show a monotonic decrease of the extension where bonds rupture with their separation along the backbone (contact order).

q-bio.BM↗

arXiv2003

Folding of Proteins in Go Models with Angular Interactions

Molecular dynamics studies of Go models of proteins with the 10-12 contact potential and the bond and dihedral angle terms indicate statistical similarities to other Go models, e.g. with the Lennard-Jones contact potentials. The folding times depend on the protein size as power laws with the exponents depending on the native structural classes. There is no dependence of the folding times on the relative contact order even though the folding scenarios are governed mostly by the contact order.

cond-mat.stat-mech↗

arXiv2002

Molecular dynamics simulations of crystallization of hard spheres

We have carried out molecular dynamics simulations of the crystallization of hard spheres modelling colloidal systems that are studied in conventional and space-based experiments. We use microscopic probes to investigate the effects of gravitational forces, polydispersity and of bounding walls on the phase structure. The simulations employed an extensive exclusive particle grid method and the type and degree of crystalline order was studied in two independent ways: by the structure factor, as in experiments, and through local rotational invariants. We present quantitative comparisons of the nucleation rates of monodisperse and polydisperse hard sphere systems and benchmark them against experimental results. We show how the presence of bounding walls leads to wall-induced nucleation and rapid crystallization and discuss the role of gravity on the dynamics of crystallization.

cond-mat↗

arXiv2002

Effects of Pore Walls and Randomness on Phase Transitions in Porous Media

We study spin models within the mean field approximation to elucidate the topology of the phase diagrams of systems modeling the liquid-vapor transition and the separation of He$^3$--He$^4$ mixtures in periodic porous media. These topologies are found to be identical to those of the corresponding random field and random anisotropy spin systems with a bimodal distribution of the randomness. Our results suggest that the presence of walls (periodic or otherwise) are a key factor determining the nature of the phase diagram in porous media.

cond-mat.stat-mech↗

arXiv2002

Universality classes in folding times of proteins

Molecular dynamics simulations in simplified models allow one to study the scaling properties of folding times for many proteins together under a controlled setting. We consider three variants of the Go models with different contact potentials and demonstrate scaling described by power laws and no correlation with the relative contact order parameter. We demonstrate existence of at least three kinetic universality classes which are correlated with the types of structure: the alpha-, alpha--beta-, and beta- proteins have the scaling exponents of about 1.7, 2.5, and 3.2 respectively. The three classes merge into one when the contact range is truncated at a 'reasonable' value. We elucidate the role of the potential associated with the chirality of a protein.

cond-mat.stat-mech↗

arXiv2002

The range of the contact interactions and the kinetics of the Go models of proteins

We consider two types of Go models of a protein (crambin) and study their kinetics through molecular dynamics simulations. In the first model, the residue -- residue contact interactions are selected based on a cutoff distance, $R_c$, between the C$_α$ atoms. The folding times depend on the value of $R_c$ strongly and non-monotonically due to the interplay between frustration and the free energy barrier for folding. This indicates a need for a physically determined set of native contacts that takes into account all the residual atoms. %%. One may accomplish it This can be accomplished by considering the van der Waals radii of the atoms and checking if %%the atoms overlap. they are found within a proper range of the van der Waals attraction. In the second model, non-native attractive contacts are added to the system. This leads to bad foldability. However, for a small number of such extra contacts there is a slight acceleration in the kinetics of folding.

cond-mat↗

arXiv2002

Prediction of Protein Secondary Structures From Conformational Biases

We use LINUS, a procedure developed by Srinivasan and Rose, to provide a physical interpretation of and to predict the secondary structures of proteins. The secondary structure type at a given site is identified by the largest conformational bias during short time simulations. We examine the rate of successful prediction as a function of temperature and the interaction window. At high temperatures, there is a large propensity for the establishment of $β$-strands whereas $α$-helices appear only when the temperature is lower than a certain threshold value. It is found that there exists an optimal temperature at which the correct secondary structures are predicted most accurately. We find that this temperature is close to the peak temperature of the specific heat. Changing the interaction window or carrying out longer simulations approaching equilibrium lead to little change in the optimal success rate. Our findings are in accord with the observation by Srinivasan and Rose that the secondary structures are mainly determined by local interactions and they appear in the early stage of folding.

cond-mat.stat-mech↗

arXiv2001

Thermal Folding and Mechanical Unfolding Pathways of Protein Secondary Structures

Mechanical stretching of secondary structures is studied through molecular dynamics simulations of a Go-like model. Force vs. displacement curves are studied as a function of the stiffness and velocity of the pulling device. The succession of stretching events, as measured by the order in which contacts are ruptured, is compared to the sequencing of events during thermal folding and unfolding. Opposite cross-correlations are found for an $α$-helix and a $β$-hairpin structure. In a tandem of two $α$-helices, the two constituent helices unravel nearly simultaneously. A simple condition for simultaneous vs. sequential unraveling of repeat units is presented.

cond-mat.soft↗

arXiv2001

Folding and Stretching in a Go-like Model of Titin

Mechanical stretching of the I27 domain of titin and of its double and triple repeats are studied through molecular dynamics simulations of a Go-like model with Lennard-Jones contact interactions. We provide a thorough characterization of the system and correlate the sequencing of the folding and unraveling events with each other and with the contact order. The roles of cantilever stiffness and pulling rate are studied. Unraveling of tandem titin structures has a serial nature. The force-displacement curves in this coarse-grained model are similar to those obtained through all atom calculations.

cond-mat.stat-mech↗

arXiv2001

Protein threading by learning

Using techniques borrowed from statistical physics and neural networks, we determine the parameters, associated with a scoring function, that are chosen optimally to ensure complete success in threading tests in a training set of proteins. These parameters provide a quantitative measure of the propensities of amino acids to be buried or exposed and to be in a given secondary structure and are a good starting point for solving both the threading and design problems.

cond-mat.soft↗