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Why Do Proteins Fold into Unique 3D Structures? And Other Questions...

  • ON THE 100th ANNIVERSARY OF THE BIRTH OF ACADEMICIAN V.I. GOLDANSKY
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Abstract

The article briefly reviews the history of the development of ideas about the dynamics of proteins and other biopolymers and notes the significant contribution of V.I. Goldansky in organizing and conducting these studies in Russia. The modern development of earlier ideas about the dynamics of biopolymers and protein folding is discussed. It is shown that folding is not an isolated problem and is related to the fundamental dynamic properties of linear polymers in the condensed phase. Analytical methods using approaches based on multidimensional geometry show that the viscosity of the medium is one of the most important factors that determines the rules for the movement of a representative point along the ultramultidimensional potential energy surface (PES). These rules lead to the concentration of trajectories in those regions of the configuration space of a macromolecule that correspond to relatively smooth PES regions, which is important for understanding the reasons for the stability of the results of calculations of large systems using the molecular dynamics (MD) method, despite the fundamental inaccuracy in determining the available force fields. This article also briefly describes a new approach to determine and study the properties of a multidimensional PES, which is based on the features of the topology of the configuration space of linear polymers (and biopolymers), symmetry with respect to permutations of identical chain links, and Morse theory for studying the topography of multidimensional surfaces. Under certain conditions, this approach gives observable analytical results for the topography of the PES and the free energy surface (FES) of a macromolecule and makes it possible to relate the rather heterogeneous results of experiments on protein folding from a unified point of view. At the same time, a new formulation appears for a number of fundamental and controversial issues related to the physical laws of the formation of living systems. In particular, a connection is traced between the temperature regime on the planet and the chemical realization of the energy of nonvalent interactions in a macromolecule, which are necessary for the formation of unique spatial structures of biopolymers.

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ACKNOWLEDGMENTS

The author thanks his colleagues at the Faculty of Mechanics and Mathematics of Moscow State University who, through, informal communication, supported his desire to continue work in the chosen direction. The author thanks M.P. Kirpichnikov for his support and attention to the work.

The support from the Interdisciplinary Scientific and Educational Schools of Moscow University “Molecular Technologies of Living Systems and Synthetic Biology” and “Brain, Cognitive Systems, and Artificial Intelligence” stimulated us to pay more attention to fundamental research.

Funding

This study could not have been undertaken without the financial support over a number of years by the Russian Foundation for Basic Research, the Russian Science Foundation, and (recently) the Russian Ministry of Science and Higher Education (grant no. 075-15-2021-1354).

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    K. V. Shaitan

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Shaitan, K.V. Why Do Proteins Fold into Unique 3D Structures? And Other Questions.... Russ. J. Phys. Chem. B 17, 550–570 (2023). https://doi.org/10.1134/S1990793123030259

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