Commentary and Perspective
Tackle “Molecular Engine” by early-career researchers
2022 Volume 19 Article ID: e190039
Details
2022 Volume 19 Article ID: e190039
The Novel Prize in Chemistry 2016 was awarded for “Design and production of molecular machines”. Many molecular machines, molecules that move like machines on the nanoscale, have been successfully synthesized and methods to produce mechanical motions have been developed. On the other hand, it has been suggested that various functions are produced by introducing the function “converting energy” to “molecular mechanical motions”. Five years ago, pioneer researchers defined such molecular machines, which have the function of energy conversion, as “Molecular Engine”. They have researched energy conversion mechanisms of biomolecular machines in detail, understood the essence and general law by physics, and synthesized artificially “Molecular Engines” by chemistry. “Molecular Engine”, design of autonomous functions through energy conversion, has buded by the orchestration of chemists, biologists, and physicists in the last five years supported by Grant-in-Aid for Scientific Research on Innovative Areas (18H05418).
This scientific concept should be passed down to the next generations for further development. To this end, early-career researchers in various research fields are trying to elucidate the energy conversion mechanism of molecular machines and to design novel ones. Here, we invite eight early-career researchers who will lead the field in the future and have a symposium at the 60th Annual Meeting of the Biophysical Society of Japan held in September 2022.
Four researchers talk about researches of biological “Molecular Engine”. By learning a detailed energy conversion mechanism from natural molecular engines, we will obtain guidelines for the design of “Molecular Engine”. Dr. Maria del Carmen Marin at the University of Tokyo focuses on the ion transport mechanism of an outward-directed light-driven H+ pumping microbial rhodopsin, PspR. From the structural insight [1], she has succeeded in creating PspR mutants which pump H+ inwardly. Dr. Ryohei Kobayashi and Dr. Akihiro Otomo present on rotary ATPases, the most abundant biological molecular engine. Dr. Kobayashi at Institute for Molecular Science reports a detailed mechanism of a regulatory protein for mitochondrial ATP synthase, IF1. One of the unique features of IF1 is the unidirectional regulation, that is, it inhibits ATP hydrolysis but does not inhibit ATP synthesis. He elucidated the unidirectional regulation system of IF1 based on the biochemical analysis [2] and single-molecule manipulation experiment. Dr. Otomo at Institute for Molecular Science revealed a rigid component in coupling between Vo and V1 motors by direct observation of stepping rotation in V-ATPase by single-molecule experiment [3]. He also reports an ongoing effort to engineer V-ATPase mutants that have non-natural ion transport properties. Dr. Kotaro Takeyasu at University of Tsukuba is working to elucidate the physiochemical mechanism of heat generation in mitochondrial respiratory chain by considering the respiratory chain as a sophisticated fuel cell reaction system. He reports the overpotentials that are converted to heat finally, at each respiratory chain complex I-IV on the basis of experimental data and the reaction mechanisms [4,5].
Two researchers talk about creations of artificial “Molecular Engine”. These studies are attempts to create novel Molecular Engines, based on knowledge of the energy conversion mechanisms that have been elucidated for biological Molecular Engines, utilizing advanced technology in synthetic chemistry and computational science. Dr. Kohei Sato at Tokyo Institute of Technology has developed a series of synthetic ion channels, using self-assembled multiblock amphiphile [6]. Here, he presents the recent studies about synthetic ion channels that can selectively transport potassium ions [7] and details of their molecular designs. Dr. Ai Niitsu at RIKEN challenges to create de novo designed peptide ion channels. She and her colleague rationally designed a stable cation-selective peptide channel by converting water-soluble de novo α-helical barrels into transmembrane one [8]. She discusses the de novo design strategy of peptide assemblies and the results of structural dynamics analyzed by electrical recordings and molecular dynamics simulations.
Two researchers talk about researches “Molecular Engine” in condensed systems and molecular assemblies. Assembled Molecular Engines exhibits characteristic physical and chemical behaviors, which are different from those of isolated ones. Understanding the molecular mechanisms underlying the assembly and function and controlling the behaviors are important topics in “Molecular Engine”. Dr. Kazusa Beppu at Aalto University studies the field of active matter physics to control the autonomous molecular collective motion. He presents a novel strategy to control active turbulence by the chirality of bacteria [9,10] and the geometric universality of active ordering, which is established from swimming bacteria to active cytoskeletons [11]. Dr. Kyohei Hisano at Tokyo Institute of Technology reports on mechanical sensors using chiral liquid crystals (CLCs) with self-organized nanostructures and tuning of molecular recovery response. This presentation focuses on a rational route for designing the optical and mechanical properties of CLC elastomers that can be applied to non-invasive, flexible mechanical sensors [12].
In this symposium, eight invited speakers talk about their own excellent researches on various types of Molecular Engines. We believe these results represent the future direction of “Molecular Engine”. We hope that this symposium encourages the fusion of research fields of the speakers and audiences and opens up new scientific frontier.
The authors thank all the speakers of this symposium and also members of a Grant-in-Aid for Scientific Research on Innovative Areas “Molecular Engine”. This work and symposium are partly supported by JSPS KAKENHI Grant Number 18H05420 to T. K. and 21K15060 to A. O.
