Biomedical subjects

Michael Slutsky

Publications and source records attributed to Michael Slutsky.

3 recordsLinked to original sources

PubMed2005

Apex exponents for polymer-probe interactions.

We consider self-avoiding polymers attached to the tip of an impenetrable probe. The scaling exponents gamma(1) and gamma(2), characterizing the number of configurations for the attachment of the polymer by one end, or at its midpoint, vary continuously with the tip's angle. These apex exponents are calculated analytically by epsilon expansion, and numerically by simulations in three dimensions. We find that when the polymer can move through the attachment point, it typically slides to one end; the apex exponents quantify the entropic barrier to threading the eye of the probe.

Biopolymers↗

PubMed2004

Kinetics of protein-DNA interaction: facilitated target location in sequence-dependent potential.

Recognition and binding of specific sites on DNA by proteins is central for many cellular functions such as transcription, replication, and recombination. In the process of recognition, a protein rapidly searches for its specific site on a long DNA molecule and then strongly binds this site. Here we aim to find a mechanism that can provide both a fast search (1-10 s) and high stability of the specific protein-DNA complex (Kd=10(-15)-10(-8) M). Earlier studies have suggested that rapid search involves sliding of the protein along the DNA. Here we consider sliding as a one-dimensional diffusion in a sequence-dependent rough energy landscape. We demonstrate that, despite the landscape's roughness, rapid search can be achieved if one-dimensional sliding is accompanied by three-dimensional diffusion. We estimate the range of the specific and nonspecific DNA-binding energy required for rapid search and suggest experiments that can test our mechanism. We show that optimal search requires a protein to spend half of its time sliding along the DNA and the other half diffusing in three dimensions. We also establish that, paradoxically, realistic energy functions cannot provide both rapid search and strong binding of a rigid protein. To reconcile these two fundamental requirements we propose a search-and-fold mechanism that involves the coupling of protein binding and partial protein folding. The proposed mechanism has several important biological implications for search in the presence of other proteins and nucleosomes, simultaneous search by several proteins, etc. The proposed mechanism also provides a new framework for interpretation of experimental and structural data on protein-DNA interactions.

Amino Acid Sequence↗

PubMed2004

Diffusion in correlated random potentials, with applications to DNA.

Many biological processes involve one-dimensional diffusion over a correlated inhomogeneous energy landscape with a correlation length xi(c). Typical examples are specific protein target location on DNA, nucleosome repositioning, or DNA translocation through a nanopore, in all cases with xi(c) approximately 10 nm. We investigate such transport processes by the mean first passage time (MFPT) formalism, and find diffusion times which exhibit strong sample to sample fluctuations. For a displacement N, the average MFPT is diffusive, while its standard deviation over the ensemble of energy profiles scales as N(3/2) with a large prefactor. Fluctuations are thus dominant for displacements smaller than a characteristic N(c) >> xi(c) : typical values are much less than the mean, and governed by an anomalous diffusion rule. Potential biological consequences of such random walks, composed of rapid scans in the vicinity of favorable energy valleys and occasional jumps to further valleys, is discussed.

Binding Sites↗