Search arXiv⌕ Search

arXiv · q-bio/0702043

Spatial Constraint Corrections to the Elasticity of dsDNA Measured with Magnetic Tweezers

Abstract

In this paper, we have studied, within a discrete WLC model, the spatial constraints in magnetic tweezers used in single molecule experiments. Two elements are involved: first, the fixed plastic slab on which is stuck the initial strand, second, the magnetic bead which pulls (or twists) the attached molecule free end. We have shown that the bead surface can be replaced by its tangent plane at the anchoring point, when it is close to the bead south pole relative to the force. We are led to a model with two parallel repulsive plates: the fixed anchoring plate and a fluctuating plate, simulating the bead, in thermal equilibrium with the system. The bead effect is a slight upper shift of the elongation, about four times smaller than the similar effect induced by the fixed plate. This rather unexpected result, has been qualitatively confirmed within the soluble Gaussian model. A study of the molecule elongation versus the countour length exhibits a significant non-extensive behaviour. The curve for short molecules (with less than 2 kbp) is well fitted by a straight line, with a slope given by the WLC model, but it does not go through the origin. The non-extensive offset gives a 15% upward shift to the elongation of a 2 kbp molecule stretched by a 0.3 pN force.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

C. Bouchiat. 2007-05-01. Spatial Constraint Corrections to the Elasticity of dsDNA Measured with Magnetic Tweezers. https://doi.org/10.1088/1742-5468%2F2007%2F06%2Fp06001

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

PocketVE: Stable and Property-Guided Structure-Based Drug Design with Variance-Exploding Diffusion

Protein-conditioned 3D molecule generation is a central challenge in structure-based drug design, requiring a balance between pocket compatibility, molecular properties, and physical geometry. We propose \textbf{PocketVE}, a protein-pocket-conditioned variance-exploding (VE) diffusion framework that couples stable coordinate denoising with inference-time property guidance. Specifically, PocketVE combines an EDM-style training and sampling setup for 3D denoising, classifier-free guidance for multi-property steering without external property classifiers, and adaptive protein perturbation as a training-time pocket regularizer. Evaluated on CrossDocked2020 under the GenBench3D protocol, PocketVE improves Valid$_{3\text{D}}$ from 58.6 to 80.6 and reduces strain energy from 457.4 to 127.9 relative to its TAGMol architectural baseline, while retaining competitive docking and molecular-property scores under moderate guidance. A guidance-scale study shows that moderate guidance gives a favorable balance between target-related objectives and geometric quality, whereas stronger guidance can degrade geometry and distributional fidelity. Pocket-permutation and PoseCheck diagnostics further support pocket-specific spatial compatibility with reduced steric conflicts. Overall, the results suggest that geometric stability and inference-time property guidance should be considered as coupled design objectives.

q-bio.BM↗

In Vivo Length Distributions as Mechanistic Fingerprints of Pathological Protein Aggregation

Modern imaging techniques can resolve individual pathological protein aggregates in postmortem human samples, providing detailed measurements of aggregate size distributions that are inaccessible with conventional bulk approaches. These distributions represent mechanistic fingerprints of the microscopic processes that generated the observed pathology, but extracting this mechanistic information requires a quantitative theoretical framework. Here, we develop the mathematical tools needed to interpret aggregate length distributions in living systems, where aggregate growth competes with active removal. We show that, across a class of models, the length distribution of sufficiently large aggregates approaches a geometric decay. Crucially, the decay rate is determined by the balance between aggregate elongation and removal, providing a direct quantitative readout of these competing processes from a single time point measurement. This enables mechanistic comparisons between healthy and diseased human samples without requiring longitudinal measurements of aggregate dynamics. We further analyse how additional aggregation and removal processes modify the observed length distributions. Together, these results establish the mathematical foundations and tools to use aggregate length distributions as an experimentally accessible route for inferring microscopic aggregation dynamics directly from human tissue.

q-bio.BM↗

Decoding enzyme-substrate interaction topology reveals principles underlying catalytic efficiency and mutational outcomes

The enzyme turnover number (kcat) defines catalytic efficiency and constrains quantitative models of metabolism, yet the molecular determinants governing kcat and its response to mutation remain poorly understood. Measurements are sparse and labor-intensive, and most computational approaches provide numerical predictions without explaining how enzyme-substrate interactions shape catalytic outcomes. A central challenge is therefore to identify the topological principles that determine where mutations act and how their functional outcomes are encoded within the enzyme-substrate interaction network. Here, we show that catalytic efficiency and mutational effects can be interpreted through enzyme-substrate interaction topology. We developed Interkcat, an interpretable bidirectional cross-attention framework that captures reciprocal coordination between protein residues and substrate atoms. Optimized on a unified benchmark, Interkcat achieves state-of-the-art predictive performance (R2 = 0.701). From its learned representations, we derive an Interaction Topology Score (ITS) that identifies sequence regions statistically enriched for mutation-sensitive sites without explicit structural inputs. We further demonstrate that higher-order topological features distinguish opposing mutational outcomes: lethal mutations disrupt coordinated networks, whereas activity-preserving or enhancing mutations retain sparse, globally organized coupling. These findings establish interaction topology as a unifying principle linking enzyme sequence, catalytic efficiency, and evolutionary perturbation.

q-bio.BM↗