Please use this identifier to cite or link to this item: http://hdl.handle.net/10995/111553
Title: On a Generalized Levinthal's Paradox: The Role of Long- and Short Range Interactions in Complex Bio-molecular Reactions, Including Protein and DNA Folding
Authors: Melkikh, A. V.
Meijer, D. K. F.
Issue Date: 2018
Publisher: Elsevier Ltd
Elsevier BV
Citation: Melkikh A. V. On a Generalized Levinthal's Paradox: The Role of Long- and Short Range Interactions in Complex Bio-molecular Reactions, Including Protein and DNA Folding / A. V. Melkikh, D. K. F. Meijer // Progress in Biophysics and Molecular Biology. — 2018. — Vol. 132. — P. 57-79.
Abstract: The current protein folding literature is reviewed. Two main approaches to the problem of folding were selected for this review: geometrical and biophysical. The geometrical approach allows the formulation of topological restrictions on folding, that are usually not taken into account in the construction of physical models. In particular, the topological constraints do not allow the known funnel-like energy landscape modeling, although most common methods of resolving the paradox are based on this method. The very paradox is based on the fact that complex molecules must reach their native conformations (complexes that result from reactions) in an exponentially long time, which clearly contradicts the observed experimental data. In this respect we considered the complexity of the reactions between ligands and proteins. On this general basis, the folding-reaction paradox was reformulated and generalized. We conclude that prospects for solving the paradox should be associated with incorporating a topology aspect in biophysical models of protein folding, through the construction of hybrid models. However, such models should explicitly include long-range force fields and local cell biological conditions, such as structured water complexes and photon/phonon/soliton waves, ordered in discrete frequency bands. In this framework, collective and coherent oscillations in, and between, macromolecules are instrumental in inducing intra- and intercellular resonance, serving as an integral guiding network of life communication: the electrome aspect of the cell. Yet, to identify the actual mechanisms underlying the bonds between molecules (atoms), it will be necessary to perform dedicated experiments to more definitely solve the particular time paradox. © 2017 Elsevier Ltd.
Keywords: DRUG DESIGN
LEVINTHAL'S PARADOX
LONG-RANGE INTERACTIONS
MOLECULAR DOCKING
NP-COMPLETENESS
PROTEIN FOLDING AND MISFOLDING
DNA
PROTEIN
RNA
CHEMISTRY
HUMAN
METABOLISM
MOLECULAR MODEL
TRANSPORT AT THE CELLULAR LEVEL
BIOLOGICAL TRANSPORT
HUMANS
MODELS, MOLECULAR
PROTEIN FOLDING
PROTEINS
URI: http://hdl.handle.net/10995/111553
Access: info:eu-repo/semantics/openAccess
SCOPUS ID: 85030464194
PURE ID: 6503531
ISSN: 0079-6107
metadata.dc.description.sponsorship: The present results were partially obtained in the frame of state task of Ministry of Education and Science of Russia 1.4539.2017/8.9.
Appears in Collections:Научные публикации, проиндексированные в SCOPUS и WoS CC

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