Biomedical subjects

D B Lukatsky

Publications and source records attributed to D B Lukatsky.

9 recordsLinked to original sources

PubMed2006

Structural similarity enhances interaction propensity of proteins.

We study statistical properties of interacting protein-like surfaces and predict two strong, related effects: (i) statistically enhanced self-attraction of proteins; (ii) statistically enhanced attraction of proteins with similar structures. The effects originate in the fact that the probability to find a pattern self-match between two identical, even randomly organized interacting protein surfaces is always higher compared with the probability for a pattern match between two different, promiscuous protein surfaces. This theoretical finding explains statistical prevalence of homodimers in protein-protein interaction networks reported earlier. Further, our findings are confirmed by the analysis of curated database of protein complexes that showed highly statistically significant overrepresentation of dimers formed by structurally similar proteins with highly divergent sequences ("superfamily heterodimers"). We suggest that promiscuous homodimeric interactions pose strong competitive interactions for heterodimers evolved from homodimers. Such evolutionary bottleneck is overcome using the negative design evolutionary pressure applied against promiscuous homodimer formation. This is achieved through the formation of highly specific contacts formed by charged residues as demonstrated both in model and real superfamily heterodimers.

Amino Acids↗

PubMed2006

Statistically enhanced self-attraction of random patterns.

In this work we develop a theory of interaction of randomly patterned surfaces as a generic prototype model of protein-protein interactions. The theory predicts that pairs of randomly superimposed identical (homodimeric) random patterns have always twice as large magnitude of the energy fluctuations with respect to their mutual orientation, as compared with pairs of different (heterodimeric) random patterns. The amplitude of the energy fluctuations is proportional to the square of the average pattern density, to the square of the amplitude of the potential and its characteristic length, and scales linearly with the area of surfaces. The greater dispersion of interaction energies in the ensemble of homodimers implies that strongly attractive complexes of random surfaces are much more likely to be homodimers, rather than heterodimers. Our findings suggest a plausible physical reason for the anomalously high fraction of homodimers observed in real protein interaction networks.

Dimerization↗

PubMed2005

Surface and bulk dissolution properties, and selectivity of DNA-linked nanoparticle assemblies.

Using a simple mean-field model, we analyze the surface and bulk dissolution properties of DNA-linked nanoparticle assemblies. We find that the dissolution temperature and the sharpness of the dissolution profiles increase with the grafting density of the single-stranded DNA "probes" on the surface of colloids. The surface grafting density is controlled by the linker occupation number, in analogy with quantum particles obeying fractional statistics. The dissolution temperature increases logarithmically with the salt concentration. This is in agreement with the experimental findings [R. Jin, G. Wu, Z. Li, C. A. Mirkin, and G. C. Schatz, J. Am. Chem. Soc. 125, 1643 (2003)]. By exploiting the unique phase behavior of DNA-coated colloids, it should be possible to detect multiple "targets" in a single experiment by essentially mapping the DNA base-pair sequence onto the phase behavior of DNA-linked nanoparticle solution.

Algorithms↗

PubMed2004

Phase behavior and selectivity of DNA-linked nanoparticle assemblies.

We propose a model that can account for the experimentally observed phase behavior of DNA-nanoparticle assemblies [J. Am. Chem. Soc. 125, 1643 (2003)]; Science 289, 1757 (2000)]]. The binding of DNA-coated nanoparticles by dissolved DNA linkers can be described by exploiting an analogy with quantum particles obeying fractional statistics. In accordance with experimental findings, we predict that the phase-separation temperature of the nanocolloids increases with the DNA coverage of the colloidal surface. Upon the addition of salt, the demixing temperature increases logarithmically with the salt concentration. Our analysis suggests an experimental strategy to map microscopic DNA sequences onto the macroscopic phase behavior of the DNA-nanoparticle solutions. Such an approach should enhance the efficiency of methods to detect (single) mutations in specific DNA sequences.

Base Sequence↗

PubMed2004

Multiple stalk formation as a pathway of defect-induced membrane fusion.

We propose that the first stage of membrane fusion need not be the formation of a single stalk. Instead, we consider a scenario for defect-induced membrane fusion that proceeds cooperatively via multiple stalk formation. The defects (stalks or pores) attract each other via membrane-mediated capillary interactions that result in a condensation transition of the defects. The resulting dense phase of stalks corresponds to the so-called fusion intermediate.

Cell Membrane↗

PubMed2003

Slow fluctuations in enhanced Raman scattering and surface roughness relaxation.

We propose an explanation for the recently measured slow fluctuations and "blinking" in the surface-enhanced Raman scattering spectrum of single molecules adsorbed on a silver colloidal particle. We suggest that these fluctuations may be related to the dynamic relaxation of the surface roughness on the nanometer scale and show that there are two classes of roughness with qualitatively different dynamics. The predictions agree with the measurements of surface roughness relaxation. Using a theoretical model for the kinetics of surface roughness relaxation in the presence of charges and optical electrical fields, we predict that the high-frequency electromagnetic field increases both the effective surface tension and the surface diffusion constant and thus accelerates the surface smoothing kinetics and time scale of the Raman fluctuations in a manner that is linear with the laser power intensity, while the addition of salt retards the surface relaxation kinetics and increases the time scale of the fluctuations. These predictions are in qualitative agreement with the Raman experiments.

Journal Article↗

PubMed2002

Charge fluctuations and counterion condensation.

We predict a condensation phenomenon in an overall neutral system, consisting of a single charged plate and its oppositely charged counterions. Based on the "two-fluid" model, in which the counterions are divided into a "free" and a "condensed" fraction, we argue that for high surface charge, fluctuations can lead to a phase transition in which a large fraction of counterions is condensed. Furthermore, we show that depending on the valence, the condensation is either a first-order or a smooth transition.

Journal Article↗

PubMed2000

Fluctuations and ordering in macroion suspensions.

We calculate the static properties of macroion density fluctuations in both bulk and in confined, strongly interacting, macroion suspensions (macroions interact via the Derjaguin-Landau-Verwey-Overbeek potential) in terms of a simple density-functional ansatz. We show how to map a strongly interacting suspension to a weakly interacting one and obtain the renormalized charge, diameter and scattering structure factors analytically. The model is extrapolated to predict crystalline order in terms of a Hansen-Verlet-type of criterion as well as an effective hard-sphere crystallization condition, and good agreement with simulations is found. The increase in correlations observed in recent experiments in two, confined layers is demonstrated.

Journal Article↗

PubMed1999

Pressure of correlated layer-charge and counterion fluctuations in charged thin films.

We predict the fluctuation contribution to the interaction between two surfaces with both mobile layer charges and delocalized counterions. The correlation (coupling) between the layer-charge fluctuations and the counterion fluctuations (around a piecewise homogeneous mean-field density profile) is taken into account in the Gaussian approximation. We find that this correlation significantly increases the magnitude of the interlayer fluctuation attraction. The counterion fluctuation pressure is calculated as a function of the intersurface distance and we show how the large and small distance limits correspond to three-dimensional (3D) and 2D fluctuations, respectively. In addition, we predict the charge density-density correlation functions. Experimental implications of the model are discussed.

Journal Article↗