Literature-based automated discovery of tumor suppressor p53 phosphorylation and inhibition by NEK2.

Scientific progress depends on formulating testable hypotheses informed by the literature. In many domains, however, this model is strained because the number of research papers exceeds human readability. Here, we developed computational assistance to analyze the biomedical literature by reading PubMed abstracts to suggest new hypotheses.

Range of interaction between DNA-bending proteins is controlled by the second-longest correlation length for bending fluctuations.

When a DNA molecule is stretched, the zero-force correlation length for its bending fluctuations-the persistence length A-bifurcates into two different correlation lengths-the shorter "longitudinal" correlation length ξ_{∥}(f) and the longer "transverse" correlation length ξ_{⊥}(f). In the high-force limit, ξ_{∥}(f)=ξ_{⊥}(f)/2=sqrt[k_{B}TA/f]/2. When DNA-bending proteins bind to the DNA molecule, there is an effective interaction between the protein-generated bends mediated by DNA elasticity and bending fluctuations.

Force-driven unbinding of proteins HU and Fis from DNA quantified using a thermodynamic Maxwell relation.

Determining numbers of proteins bound to large DNAs is important for understanding their chromosomal functions. Protein numbers may be affected by physical factors such as mechanical forces generated in DNA, e.g.

Intrinsic and force-generated cooperativity in a theory of DNA-bending proteins.

We study a statistical-mechanical model of the binding of DNA-bending proteins to the double helix including applied tension and binding cooperativity effects. Intrinsic cooperativity of binding sharpens force-extension curves and causes enhancement of fluctuation of extension and protein occupation. This model also allows us to estimate the intrinsic cooperativity in experiments by measuring the peak value of the slope of extension versus chemical-potential curves.

Maxwell relations for single-DNA experiments: Monitoring protein binding and double-helix torque with force-extension measurements.

Single-DNA stretching and twisting experiments provide a sensitive means to detect binding of proteins, via detection of their modification of DNA mechanical properties. However, it is often difficult or impossible to determine the numbers of proteins bound in such experiments, especially when the proteins interact nonspecifically (bind stably at any sequence position) with DNA. Here we discuss how analogs of the Maxwell relations of classical thermodynamics may be defined and used to determine changes in numbers of bound proteins, from measurements of extension as a function of bulk protein concentration.