Physics-based potentials for the coupling between backbone- and side-chain-local conformational states in the United Residue (UNRES) force field for protein simulations

Adam Sieradzan , Paweł Krupa , Harold A. Scheraga , Józef Adam Liwo , Cezary Czaplewski


The UNited RESidue (UNRES) model of polypeptide chains is a coarse-grained model in which each amino-acid residue is reduced to two interaction sites, namely, a united peptide group (p) located halfway between the two neighboring α-carbon atoms (Cαs), which serve only as geometrical points, and a united side chain (SC) attached to the respective Cα. Owing to this simplification, millisecond molecular dynamics simulations of large systems can be performed. While UNRES predicts overall folds well, it reproduces the details of local chain conformation with lower accuracy. Recently, we implemented new knowledge-based torsional potentials (Krupa et al. J. Chem. Theory Comput. 2013, 9, 4620–4632) that depend on the virtual-bond dihedral angles involving side chains: Cα···Cα···Cα···SC (τ(1)), SC···Cα···Cα···Cα (τ(2)), and SC···Cα···Cα···SC (τ(3)) in the UNRES force field. These potentials resulted in significant improvement of the simulated structures, especially in the loop regions. In this work, we introduce the physics-based counterparts of these potentials, which we derived from the all-atom energy surfaces of terminally blocked amino-acid residues by Boltzmann integration over the angles λ(1) and λ(2) for rotation about the Cα···Cα virtual-bond angles and over the side-chain angles χ. The energy surfaces were, in turn, calculated by using the semiempirical AM1 method of molecular quantum mechanics. Entropy contribution was evaluated with use of the harmonic approximation from Hessian matrices. One-dimensional Fourier series in the respective virtual-bond-dihedral angles were fitted to the calculated potentials, and these expressions have been implemented in the UNRES force field. Basic calibration of the UNRES force field with the new potentials was carried out with eight training proteins, by selecting the optimal weight of the new energy terms and reducing the weight of the regular torsional terms. The force field was subsequently benchmarked with a set of 22 proteins not used in the calibration. The new potentials result in a decrease of the root-mean-square deviation of the average conformation from the respective experimental structure by 0.86 Å on average; however, improvement of up to 5 Å was observed for some proteins.
Author Adam Sieradzan (FCh / DTCh / LMM)
Adam Sieradzan,,
- Laboratory of Molecular Modeling
, Paweł Krupa (FCh / DTCh / LSP)
Paweł Krupa,,
- Laboratory of Simulation of Polymers
, Harold A. Scheraga - [Cornell University]
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, (A 40 pkt)
Issue year2015
Publication size in sheets0.7
ASJC Classification1606 Physical and Theoretical Chemistry; 1706 Computer Science Applications
Languageen angielski
Score (nominal)40
Score sourcejournalList
ScoreMinisterial score = 40.0, 29-05-2020, ArticleFromJournal
Ministerial score (2013-2016) = 40.0, 29-05-2020, ArticleFromJournal
Publication indicators WoS Citations = 28; Scopus Citations = 29; Scopus SNIP (Source Normalised Impact per Paper): 2015 = 1.589; WoS Impact Factor: 2015 = 5.301 (2) - 2015=5.756 (5)
Citation count*40 (2020-05-24)
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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.
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