61HIGHLIGHTS 2020

Rapidly Forming Early Intermediate Structures Dictate the Pathway of Capsid Assembly, R. Asor (a), C.J. Schlicksup (b), Z. Zhao (b), A. Zlotnick (b) and U. Raviv (a),

J. Am. Chem. Soc. 142, 7868 (2020); https://doi.org/10.1021/jacs.0c01092. (a) Institute of Chemistry, The Hebrew University of Jerusalem (Israel)

(b) Molecular and Cellular Biochemistry Department, Indiana University (USA)

[1] R. Asor et al., ACS Nano 13, 7, 7610-7626 (2019). [2] A. Ginsburg et al., J. Appl. Cryst. 52, 219-242 (2019). [3] R. Asor et al., J. Am. Chem. Soc. 142, 17, 7868-7882 (2020).

THIOL LAYERS WITHOUT GOLD SUPPORT Covering a solid with a thin monolayer, typically using gold film, can dramatically change the properties of the material. Surface X-ray diffraction and other techniques have been used to show that a new way of creating monolayers by direct application on a muscovite substrate leads to extremely flat monolayers.

PRINCIPAL PUBLICATION AND AUTHORS

REFERENCES

The pathway of HBV capsid assembly was found to be dictated by early intermediates. At mild, biologically relevant, dimer dimer association free energy, assembly started after a lag phase of 10 s and appeared to be a two-state reaction with Cp149 dimers and complete T = 4 capsids. The data are consistent with multiple reversible steps, allowing the reaction to follow the minimum free-energy path, at which the most stable and compact intermediate structures are dominant. Under aggressive assembly conditions, the dimer concentration rapidly

decreased without any measurable lag phase. An array of intermediates containing between 7 and 35 dimers accumulated within 250 msec, after which T = 3 and T = 4 capsids were detected [3].

These findings show that the dimer dimer association free energy control the earliest steps of the reaction, which dictate the subsequent assembly pathway, and may provide strategies for understanding, regulating, and designing assembly of protein cages.

Fig. 45: a-b) Grand canonical free energy surface heat maps (in kBT units) in the plane of degree of connectivity versus the size of intermediates (in dimers) for T = 4 capsid at the onset of the assembly reactions. Heat maps correspond to (a) mild and (b) aggressive conditions. Degree of connectivity measures the stability of an intermediate, based on the number of interdimer interactions. c) Initial grand canonical free energy change, along the minimum free energy path (see panel (a)). d) Illustration of HBV capsid assembly pathways at different solution conditions.

Thin monolayer films have been of human interest since Babylonian times, when thin oily layers were created on the surface of water for divination [1]. This type of monolayer was later studied by Agnes Puckles, who published on the topic with the help of Lord Rayleigh in 1891 [2].

This laid the groundwork for a scientific field that would later also include Langmuir-Blodgett films. With the invention of scanning probe microscopy, single molecules and monolayers were finally directly observable, which made for ever-increasing possibilities and a growing