Alexander Tenenbaum

Molecular dynamics simulation of intrinsically disordered proteins

Intrinsically disordered proteins are biomolecules that do not have a definite 3D structure; therefore, their dynamical simulation cannot start from a known list of atomistic positions, such as a Protein Data Bank file. We describe a method to start a computer simulation of these proteins. The first step of the procedure is the creation of a multi-rod configuration of the molecule, derived from its primary sequence. This structure is dynamically evolved in vacuo until its gyration radius reaches the experimental average value; at this point solvent molecules, in explicit or implicit implementation, are added to the protein and a regular molecular dynamics simulation follows. We have applied this procedure to the simulation of tau, one of the largest totally disordered proteins.

Temporary secondary structures in tau, an intrinsically disordered protein

The tau protein belongs to the category of intrinsically disordered proteins, which in their native state do not have an average stable structure and fluctuate between many conformations. In its physiological state, tau helps nucleating and stabilising the microtubules in the axons of the neurons. On the other hand, the same tau is involved in the development of Alzheimer disease, when it aggregates in paired helical filaments forming fibrils, which form insoluble tangles. The beginning of the pathological aggregation of tau has been attributed to a local transition of protein portions from random coil to a β-sheet. These structures would very likely be transient; therefore, we performed a molecular dynamics simulation of tau to gather information on the existence of segments of tau endowed with a secondary structure. We combined the results of our simulation with small-angle X-ray scattering experimental data to extract from the dynamics a set of most probable conformations of tau. The analysis of these conformations highlights the presence of transient secondary structures such as turns, β-bridges, β-sheets and α-helices. It also shows that a large segment of the N-terminal region is found near the repeats domain in a globular-like shape.

On the unconventional amide I band in acetanilide

Abstract We developed a new model to study the molecular dynamics of the acetanilide (ACN) crystal by computer simulation. Low-frequency oscillations of the molecules as a whole were considered with high-frequency vibrations of the amidic degrees of freedom involved in hydrogen bonding. The low-temperature power spectrum has two peaks, shifted by 15 cm −1 , in the region of the amide I band: one of them corresponds to the so-called anomalous amide I band in the IR and Raman spectra of ACN. We found that this peak is due to the coupling of the low-frequency motion in the chain of molecules with the motion of the hydrogen-bonded protons, at variance with current suggestions.

Transient tertiary structures in tau, an intrinsically disordered protein

An intrinsically disordered protein (IDP) does not have a definite 3D structure, and because of its highly flexible nature it evolves dynamically in very large and diverse regions of the phase space. A standard molecular dynamics run can sample only a limited region of the latter; even though this kind of simulation may be effective in sampling local temporary secondary structures, it is not sufficient to highlight properties that require a larger sampling of the phase space to be detected, like transient tertiary structures. But if the structure of an IDP is dynamically evolved using metadynamics (an algorithm that keeps track of the regions of the phase space already sampled), the system can be forced to wander in a much larger region of the phase space. We have applied this procedure to the simulation of tau, one of the largest totally disordered proteins. Combining the results of the simulation with small-angle X-ray scattering yields a significant improvement in the sampling of the phase space in comparison with standard molecular dynamics, and provides evidence of extended hairpin- and paperclip-like transient tertiary structures of the molecule. The more persistent tertiary pattern is a hairpin folding encompassing part of the N-terminal, the proline-rich domain, the former repeat and a functionally relevant part of the second repeat.

Molecular dynamics on APE100

Abstract We have studied portability, efficiency and accuracy of a standard Molecular Dynamics simulation on the SIMD parallel computer APE100. Computing speed performance and physical system size range have been analyzed and compared with those of a conventional computer. Short range and long range potentials have been considered, and the comparative advantage of different simulation approaches has been assessed. For long range potentials, APE turns out to be faster than a conventional computer; large systems can be conveniently simulated using either the cloning approach (up to ∼ 10 5 particles) or a domain decomposition with the systolic method. In the case of short range potentials and systems with diffusion (like a liquid), APE is convenient only when using a large number of processors. In a special case (a crystal without diffusion), a specific domain decomposition technique with frames makes APE advantageous for intermediate and large systems. Using the latter technique we have studied in detail the effect of different numerical error sources, and compared the accuracy of APE with that of a conventional computer.

Nuclear reactions from lattice collapse in a cold fusion model

Abstract We propose a model which accounts for cold fusion processes on the basis of a lattice collapse, induced in a deuterated metal by a thermodynamic instability. A deuteron drag phenomenon enhances the nuclear reaction yield. Neutron emission is given as a function of thermodynamic parameters of the metal-deuterium system.

Nuclear effects in the collapsing lattice model for deuterated palladium: New results

The collapsing lattice model is developed based on the assumption that rapid material transitions in deuterated metals can induce a coherent release of elastic energy. (AIP)

Coherence angles and coherence times in Hamiltonian systems with many degrees of freedom

The coexistence of ordered and chaotic dynamics in one and the same system has been detected already several years ago. A thorough description of a complex dynamical system, both from a mechanical and from a statistical point of view, requires the determination of the level of order and chaoticity of each single degree of freedom (DOF). We have introduced in a recent paper a new diagnostic tool to analyse the chaoticity of single DOFs or groups of DOFs: the coherence angles, which measure the angular distance between any physically relevant direction and the direction of maximum expansion in the tangent space. They allow at the same time a detailed characterization and a synoptic view of the dynamical behaviour of a system with many DOFs, but lack resolution among the most ordered DOFs when their number is very large. We present here a method allowing the attribution to each DOF (or group of DOFs) of a characteristic coherence time, which overcomes this lack of resolution. In phase space regions characterized by a highly chaotic dynamics, the coherence times are similar. On the other hand, in regions where the dynamics is weakly chaotic, the coherence times show relevant differences in the dynamical behaviour of different groups of DOFs.

Vibrational Properties and Energy Transport in Acetanilide by Molecular Dynamics

Soon after Careri, Scott and co-workers assigned the anomalous low-temperature amide I band of ACN to a self trapped state similar to a Davydov soliton1, 2, we started computer experiments on a model of ACN with at least three goals: a) to set up molecular models of the interactions present in the real crystal, simple but sufficient to elucidate the degrees of freedom involved in some relevant nonlinear effects; b) to explore the occurence of a stochastic transition, also to be related to peculiarities of the ACN dynamics; c) to study the transport of energy along chains of ACN molecules.

Lattice Instability and Cold Fusion in Deuterated Metals

In this paper, we present a model which could help in explaining cold fusion processes on the basis of a lattice collapse in a deuterated metal. We shall show that a thermodynamic Instability can, under favourable conditions, trigger a coherent and concentric displacement flow in the metal, which can accumulate in a small region the excess elastic energy originally distributed in an expanded domain. Conditions allowing nuclear fusion processes can thus be created.