Prediction of Protein Structure by Template-Based Modeling Combined with the UNRES Force Field

Krupa, Paweł; Mozolewska, Magdalena A.; Joo, Keehyoung; Lee, Jooyoung; Czaplewski, Cezary; Liwo, Adam

doi:10.1021/acs.jcim.5b00117

Cited by 16 publications

(37 citation statements)

References 51 publications

(143 reference statements)

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“…The first one was a two-domain target T0663 (treated by the Cornell-Gdansk group) (He et al, 2013), and the second one was T0740 (treated by the wfCPUNK group within the WeFold initiative) (Khoury et al, 2014); in the second prediction exercise, UNRES was supplemented with contact-prediction restraints. In the CASP10 experiment, we proved that the UNRES force field is a very good tool to predict the orientation of the domains for the 2-fold symmetry target T0663 (He et al, 2013) that was further confirmed by post-CASP tests with use of restraints within the domains, but not between them (Krupa et al, 2015).…”

Section: Introductionmentioning

confidence: 64%

Performance of protein-structure predictions with the physics-based UNRES force field in CASP11

et al. 2016

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Summary: Participating as the Cornell-Gdansk group, we have used our physics-based coarsegrained UNited RESidue (UNRES) force field to predict protein structure in the 11th Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction (CASP11). Our methodology involved extensive multiplexed replica exchange simulations of the target proteins with a recently improved UNRES force field to provide better reproductions of the local structures of polypeptide chains. All simulations were started from fully extended polypeptide chains, and no external information was included in the simulation process except for weak restraints on secondary structure to enable us to finish each prediction within the allowed 3-week time window. Because of simplified UNRES representation of polypeptide chains, use of enhanced sampling methods, code optimization and parallelization and sufficient computational resources, we were able to treat, for the first time, all 55 human prediction targets with sizes from 44 to 595 amino acid residues, the average size being 251 residues. Complete structures of six singledomain proteins were predicted accurately, with the highest accuracy being attained for the T0769, for which the CaRMSD was 3.8 Å for 97 residues of the experimental structure. Correct structures were also predicted for 13 domains of multi-domain proteins with accuracy comparable to that of the best template-based modeling methods. With further improvements of the UNRES force field that are now underway, our physics-based coarse-grained approach to protein-structure prediction will eventually reach global prediction capacity and, consequently, reliability in simulating protein structure and dynamics that are important in biochemical processes. Availability and Implementation: Freely available on the web at

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Section: Introductionmentioning

confidence: 64%

Performance of protein-structure predictions with the physics-based UNRES force field in CASP11

et al. 2016

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“…on C α atoms to ensure high stability of β ‐sheet core of Fn3 domain of human contactin 1 and the I27 titin domain were preformed. UNRES force field performs very well when structure‐based restraints are combined with physics‐based energy function . The other simulation parameters were the same as without restrains, apart from the wider range of forces, up to 14.0 (kcal × mol

^{- 1} \times

Å – 1 ), had to be used.…”

Section: Methodsmentioning

confidence: 99%

Introduction of steered molecular dynamics into UNRES coarse‐grained simulations package

Sieradzan

Jakubowski

2017

J Comput Chem

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In this article, an implementation of steered molecular dynamics (SMD) in coarse-grain UNited RESidue (UNRES) simulations package is presented. Two variants of SMD have been implemented: with a constant force and a constant velocity. The huge advantage of SMD implementation in the UNRES force field is that it allows to pull with the speed significantly lower than the accessible pulling speed in simulations with all-atom representation of a system, with respect to a reasonable computational time. Therefore, obtaining pulling speed closer to those which appear in the atomic force spectroscopy is possible. The newly implemented method has been tested for behavior in a microcanonical run to verify the influence of introduction of artificial constrains on keeping total energy of the system. Moreover, as time dependent artificial force was introduced, the thermostat behavior was tested. The new method was also tested via unfolding of the Fn3 domain of human contactin 1 protein and the I27 titin domain. Obtained results were compared with Gø-like force field, all-atom force field, and experimental results. © 2017 Wiley Periodicals, Inc.

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“…The log‐Gaussian restraints on the distances, virtual‐bond angles, virtual‐bond‐dihedral angles, and local coordinates of side‐chain centers are expressed by eqs. , respectively; these terms originate from the MODELLER restraint pseudo‐energy function and are similar to those which were implemented in our earlier work

V_{normald}^{(G)} = - \sum_{i < j} \ln true{\sum_{m = 1}^{M} \exp true[- \frac{1}{2} {true(\frac{d_{i j} - d_{i j}^{(m)}}{σ_{d_{i j}}^{(m)}} true)}^{2} true] true}

V_{γ}^{(G)} = - \sum_{i} \ln true{\sum_{m = 1}^{M} \exp true[- \frac{1}{2} {true(\frac{γ_{i} - γ_{i}^{(m)}}{σ_{γ_{i}}^{(m)}} true)}^{2} true] true}

V_{θ}^{(G)} = - \sum_{i} \ln true{\sum_{m = 1}^{M} \exp true[- \frac{1}{2} true(\frac{θ_{i} - θ_{i}^{(m)}}{σ_{θ_{i}}^{(m)}}

…”

Section: Methodsmentioning

confidence: 99%

“…Recently, we proposed a hybrid approach to protein‐structure prediction, in which restrained conformational search is carried out with the use of the physics‐based coarse‐grained UNRES force field, subject to the distance‐ and angle‐restraints from knowledge‐based models. This approach is an extension of the application of the UNRES force field beyond unrestrained (physics‐based) simulations of protein structure and dynamics.…”

Section: Introductionmentioning

confidence: 99%

“…As opposed to model refinement with MODELLER, use of coarse‐grained representation of polypeptide chains enables us to carry out an extensive conformational search and restraints are imposed not on the whole structure but only on its parts that are predicted by the knowledge‐based methods with high confidence; these parts are domains or fragments for which most of the knowledge‐based methods predict a similar structure. We found that this approach often results in major improvements of the obtained models with respect to the parent models, because the restraints most compatible with the UNRES energy function are selected and, moreover, UNRES can build the part of structure which is undefined in the parent models . However, as all restrained simulations which aim at extensive search of the conformational space, the approach is potentially liable to ergodicity problems, because of the appearance of barriers due to the introduction of the restraints.…”

Section: Introductionmentioning

confidence: 99%

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Ergodicity and model quality in template‐restrained canonical and temperature/Hamiltonian replica exchange coarse‐grained molecular dynamics simulations of proteins

et al. 2017

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Molecular simulations restrained to single or multiple templates are commonly used in protein-structure modeling. However, the restraints introduce additional barriers, thus impairing the ergodicity of simulations, which can affect the quality of the resulting models. In this work, the effect of restraint types and simulation schemes on ergodicity and model quality was investigated by performing template-restrained canonical molecular dynamics (MD), multiplexed replica-exchange molecular dynamics, and Hamiltonian replica exchange molecular dynamics (HREMD) simulations with the coarse-grained UNRES force field on nine selected proteins, with pseudo-harmonic log-Gaussian (unbounded) or Lorentzian (bounded) restraint functions. The best ergodicity was exhibited by HREMD. It has been found that non-ergodicity does not affect model quality if good templates are used to generate restraints. However, when poor-quality restraints not covering the entire protein are used, the improved ergodicity of HREMD can lead to significantly improved protein models. © 2017 Wiley Periodicals, Inc.

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Prediction of Protein Structure by Template-Based Modeling Combined with the UNRES Force Field

Cited by 16 publications

References 51 publications

Performance of protein-structure predictions with the physics-based UNRES force field in CASP11

Performance of protein-structure predictions with the physics-based UNRES force field in CASP11

Introduction of steered molecular dynamics into UNRES coarse‐grained simulations package

Ergodicity and model quality in template‐restrained canonical and temperature/Hamiltonian replica exchange coarse‐grained molecular dynamics simulations of proteins

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