3
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Studies on Molecular Dynamics of Intrinsically Disordered Proteins and Their Fuzzy Complexes: A Mini-Review

      review-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          The molecular dynamics (MD) method is a promising approach toward elucidating the molecular mechanisms of intrinsically disordered regions (IDRs) of proteins and their fuzzy complexes. This mini-review introduces recent studies that apply MD simulations to investigate the molecular recognition of IDRs. Firstly, methodological issues by which MD simulations treat IDRs, such as developing force fields, treating periodic boundary conditions, and enhanced sampling approaches, are discussed. Then, several examples of the applications of MD to investigate molecular interactions of IDRs in terms of the two kinds of complex formations; c oupled-folding and binding and fuzzy complex. MD simulations provide insight into the molecular mechanisms of these binding processes by sampling conformational ensembles of flexible IDRs. In particular, we focused on all-atom explicit-solvent MD simulations except for studies of higher-order assembly of IDRs. Recent advances in MD methods, and computational power make it possible to dissect the molecular details of realistic molecular systems involving the dynamic behavior of IDRs.

          Related collections

          Most cited references76

          • Record: found
          • Abstract: found
          • Article: not found

          Intrinsically unstructured proteins: re-assessing the protein structure-function paradigm.

          A major challenge in the post-genome era will be determination of the functions of the encoded protein sequences. Since it is generally assumed that the function of a protein is closely linked to its three-dimensional structure, prediction or experimental determination of the library of protein structures is a matter of high priority. However, a large proportion of gene sequences appear to code not for folded, globular proteins, but for long stretches of amino acids that are likely to be either unfolded in solution or adopt non-globular structures of unknown conformation. Characterization of the conformational propensities and function of the non-globular protein sequences represents a major challenge. The high proportion of these sequences in the genomes of all organisms studied to date argues for important, as yet unknown functions, since there could be no other reason for their persistence throughout evolution. Clearly the assumption that a folded three-dimensional structure is necessary for function needs to be re-examined. Although the functions of many proteins are directly related to their three-dimensional structures, numerous proteins that lack intrinsic globular structure under physiological conditions have now been recognized. Such proteins are frequently involved in some of the most important regulatory functions in the cell, and the lack of intrinsic structure in many cases is relieved when the protein binds to its target molecule. The intrinsic lack of structure can confer functional advantages on a protein, including the ability to bind to several different targets. It also allows precise control over the thermodynamics of the binding process and provides a simple mechanism for inducibility by phosphorylation or through interaction with other components of the cellular machinery. Numerous examples of domains that are unstructured in solution but which become structured upon binding to the target have been noted in the areas of cell cycle control and both transcriptional and translational regulation, and unstructured domains are present in proteins that are targeted for rapid destruction. Since such proteins participate in critical cellular control mechanisms, it appears likely that their rapid turnover, aided by their unstructured nature in the unbound state, provides a level of control that allows rapid and accurate responses of the cell to changing environmental conditions. Copyright 1999 Academic Press.
            Bookmark
            • Record: found
            • Abstract: not found
            • Article: not found

            Principles that govern the folding of protein chains.

            C ANFINSEN (1973)
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The protein-folding problem, 50 years on.

              The protein-folding problem was first posed about one half-century ago. The term refers to three broad questions: (i) What is the physical code by which an amino acid sequence dictates a protein's native structure? (ii) How can proteins fold so fast? (iii) Can we devise a computer algorithm to predict protein structures from their sequences? We review progress on these problems. In a few cases, computer simulations of the physical forces in chemically detailed models have now achieved the accurate folding of small proteins. We have learned that proteins fold rapidly because random thermal motions cause conformational changes leading energetically downhill toward the native structure, a principle that is captured in funnel-shaped energy landscapes. And thanks in part to the large Protein Data Bank of known structures, predicting protein structures is now far more successful than was thought possible in the early days. What began as three questions of basic science one half-century ago has now grown into the full-fledged research field of protein physical science.
                Bookmark

                Author and article information

                Contributors
                Journal
                Comput Struct Biotechnol J
                Comput Struct Biotechnol J
                Computational and Structural Biotechnology Journal
                Research Network of Computational and Structural Biotechnology
                2001-0370
                13 June 2019
                2019
                13 June 2019
                : 17
                : 712-720
                Affiliations
                [a ]College of Life Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, Japan
                [b ]Graduate School of Life Sciences, Ritsumeikan University, 1-1-1 Noji-higashi, Kusatsu, Shiga 525-8577, Japan
                [c ]Graduate School of Simulation Studies, University of Hyogo, 7-1-28 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
                Author notes
                [* ]Corresponding author. ktkshr@ 123456fc.ritsumei.ac.jp
                Article
                S2001-0370(19)30067-4
                10.1016/j.csbj.2019.06.009
                6603302
                31303975
                26d08355-6096-4209-a697-a6e79ecfbd97
                © 2019 The Authors

                This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).

                History
                : 1 March 2019
                : 29 May 2019
                : 11 June 2019
                Categories
                Review Article

                Comments

                Comment on this article