Improvement of the treatment of loop structures in the UNRES force field by inclusion of coupling between backbone- and side-chain-local conformational states

Paweł Krupa , Adam Sieradzan , S. Rackovsky , Maciej Baranowski , Stanisław Ołdziej , Harold A. Scheraga , Józef Adam Liwo , Cezary Czaplewski


The UNited RESidue (UNRES) coarse-grained model of polypeptide chains, developed in our laboratory, enables us to carry out millisecond-scale molecular-dynamics simulations of large proteins e ff ectively. It performs well in ab initio predictions of protein structure, as demonstrated in the last Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP10). However, the resolution of the simulated structure is too coarse, especially in loop regions, which results from insu ffi cient speci fi city of the model of local interactions. To improve the representation of local interactions, in this work, we introduced new side-chain-backbone correlation potentials, derived from a statistical analysis of loop regions of 4585 proteins. To obtain su ffi cient statistics, we reduced the set of amino- acid-residue types to fi ve groups, derived in our earlier work on structurally optimized reduced alphabets [Solis, A. D.; Rackovsky, S. Proteins: Struct., Func., Bioinf. , 2000 , 38, 149 − 164], based on a statistical analysis of the properties of amino-acid structures. The new correlation potentials are expressed as one-dimensional Fourier series in the virtual-bond-dihedral angles involving side- chain centroids. The weight of these new terms was determined by a trial-and-error method, in which Multiplexed Replica Exchange Molecular Dynamics (MREMD) simulations were run on selected test proteins. The best average root-mean-square deviations (RMSDs) of the calculated structures from the experimental structures below the folding-transition temperatures were obtained with the weight of the new side-chain-backbone correlation potentials equal to 0.57. The resulting conformational ensembles were analyzed in detail by using the Weighted Histogram Analysis Method (WHAM) and Ward ’ s minimum-variance clustering. This analysis showed that the RMSDs from the experimental structures dropped by 0.5 Å on average, compared to simulations without the new terms, and the deviation of individual residues in the loop region of the computed structures from their counterparts in the experimental structures (after optimum superposition of the calculated and experimental structure) decreased by up to 8 Å. Consequently, the new terms improve the representation of local structure.
Author Paweł Krupa (FCh / DTCh / LSP)
Paweł Krupa,,
- Laboratory of Simulation of Polymers
, Adam Sieradzan (FCh / DTCh / LMM)
Adam Sieradzan,,
- Laboratory of Molecular Modeling
, S. Rackovsky
S. Rackovsky,,
, Maciej Baranowski (IFB)
Maciej Baranowski,,
- Intercollegiate Faculty of Biotechnology UG
, Stanisław Ołdziej (IFB / IB / LBiopolS)
Stanisław Ołdziej,,
- Laboratory of Biopolymers Structure
, Harold A. Scheraga
Harold A. Scheraga,,
, Józef Adam Liwo (FCh / DTCh / LMM)
Józef Adam Liwo,,
- Laboratory of Molecular Modeling
, Cezary Czaplewski (FCh / DTCh / LSP)
Cezary Czaplewski,,
- Laboratory of Simulation of Polymers
Journal seriesJournal of Chemical Theory and Computation, ISSN 1549-9618, e-ISSN 1549-9626, (A 40 pkt)
Issue year2013
Publication size in sheets0.6
Languageen angielski
Score (nominal)40
ScoreMinisterial score = 40.0, 29-11-2018, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 29-11-2018, ArticleFromJournal
Publication indicators WoS Impact Factor: 2013 = 5.31 (2) - 2013=6.205 (5)
Citation count*34 (2019-03-22)
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* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.