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Title: Direct Probing of Protein-Protein Interactions

This project aimed to establish feasibility of using experimental techniques based on direct measurements of interaction forces on the single molecule scale to characterize equilibrium interaction potentials between individual biological molecules. Such capability will impact several research areas, ranging from rapid interaction screening capabilities to providing verifiable inputs for computational models. It should be one of the enabling technologies for modern proteomics research. This study used a combination of Monte-Carlo simulations, theoretical considerations, and direct experimental measurements to investigate two model systems that represented typical experimental situations: force-induced melting of DNA rigidly attached to the tip, and force-induced unbinding of a protein-antibody pair connected to flexible tethers. Our results establish that for both systems researchers can use force spectroscopy measurements to extract reliable information about equilibrium interaction potentials. However, the approaches necessary to extract these potentials in each case--Jarzynski reconstruction and Dynamic Force Spectroscopy--are very different. We also show how the thermodynamics and kinetics of unbinding process dictates the choice between in each case.
Authors:
; ;
Publication Date:
OSTI Identifier:
15015174
Report Number(s):
UCRL-TR-210446
TRN: US0501648
DOE Contract Number:
W-7405-ENG-48
Resource Type:
Technical Report
Resource Relation:
Other Information: PBD: 10 Mar 2005
Research Org:
Lawrence Livermore National Lab., Livermore, CA (US)
Sponsoring Org:
US Department of Energy (US)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; 59 BASIC BIOLOGICAL SCIENCES; 75 CONDENSED MATTER PHYSICS, SUPERCONDUCTIVITY AND SUPERFLUIDITY; DNA; KINETICS; MELTING; SPECTROSCOPY; THERMODYNAMICS