Modeling protein structures with the coarse-grained UNRES force field in the CASP14 experiment

Antoniak, Anna; Biskupek, Iga; Bojarski, Krzysztof K.; Czaplewski, Cezary; Giełdoń, Artur; Kogut, Mateusz; Kogut, Małgorzata M.; Krupa, Paweł; Lipska, Agnieszka G.; Liwo, Adam; Lubecka, Emilia A.; Marcisz, Mateusz; Maszota‐Zieleniak, Martyna; Samsonov, Sergey A.; Sieradzan, Adam K.; Ślusarz, Magdalena J.; Ślusarz, Rafał; Wesołowski, Patryk; Ziȩba, Karolina

doi:10.1016/j.jmgm.2021.108008

Cited by 20 publications

(29 citation statements)

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“…It is regularly being tested in the biannual Community Wide Experiments on the Critical Assessment of Techniques for Protein Structure Prediction (CASP) [ 35 ]; see Ref. [ 36 ] for recent results. It has also been used with success to study the aggregation of the A

amyloidogenic peptides [ 37 , 38 , 39 ] and the association of the A

and Tau peptides [ 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model

et al. 2022

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The UNited RESidue (UNRES) model of polypeptide chains was applied to study the association of 20 peptides with sizes ranging from 6 to 32 amino-acid residues. Twelve of those were potentially aggregating hexa- or heptapeptides excised from larger proteins, while the remaining eight contained potentially aggregating sequences, functionalized by attaching larger ends rich in charged residues. For 13 peptides, the experimental data of aggregation were used. The remaining seven were synthesized, and their properties were measured in this work. Multiplexed replica-exchange simulations of eight-chain systems were conducted at 12 temperatures from 260 to 370 K at concentrations from 0.421 to 5.78 mM, corresponding to the experimental conditions. The temperature profiles of the fractions of monomers and octamers showed a clear transition corresponding to aggregate dissociation. Low simulated transition temperatures were obtained for the peptides, which did not precipitate after incubation, as well as for the H-GNNQQNY-NH2 prion–protein fragment, which forms small fibrils. A substantial amount of inter-strand β-sheets was found in most of the systems. The results suggest that UNRES simulations can be used to assess peptide aggregation except for glutamine- and asparagine-rich peptides, for which a revision of the UNRES sidechain–sidechain interaction potentials appears necessary.

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amyloidogenic peptides [ 37 , 38 , 39 ] and the association of the A

and Tau peptides [ 40 , 41 ].…”

Section: Introductionmentioning

confidence: 99%

Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model

et al. 2022

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“…We used the four‐stage protocol developed in our earlier work for protein‐structure modeling 35,52 . In the first stage, HREMD simulations with the UNRES force field with geometry restraints from NMR (see Sections 2.2 and 2.4), as well as control MREMD simulations, were carried out.…”

Section: Methodsmentioning

confidence: 99%

“…The final statistical weights of the conformations were calculated for w NMR = 1. The temperatures and the weights were selected to maximize the number of walks in the weight space, by using a variant of the Hansmann algorithm, 55 adapted to the weight space 35 . The unrestrained UNRES/MREMD simulations were carried out with the same set of 12 temperatures as above, four trajectories run at each temperature (48 replicas total).…”

Section: Methodsmentioning

confidence: 99%

“…We used the four-stage protocol developed in our earlier work for protein-structure modeling. 35,52 In the first stage, HREMD simulations with the UNRES force field with geometry restraints from NMR (see Sections 2.2 and 2.4), as well as control MREMD simulations, were carried out. In the second stage, the results of the simulations were processed with the binless Weighted-Histogram Analysis Method (WHAM) 43,53 to compute the conformational weights to calculate the statistical weight (probability) of each structure of the last section of HREMD simulation.…”

Section: Unres-based Simulation Protocolmentioning

confidence: 99%

“…Two NMR-assisted targets, N1077 and N1088, with highlyambiguous restraints, were also released in CASP14, 23 of which the models of N1088 were evaluated, while the structure of N1077 was not available by the conclusion of CASP14. In CASP14 we used a preliminary version of the methodology described in this work, obtaining top-ranked models 23,35 However, because the structure of neither of these two targets has been released yet we did not include these proteins in the present study.…”

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confidence: 99%

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A coarse‐grained approach toNMR‐data‐assisted modeling of protein structures

Lubecka

Liwo

2022

J Comput Chem

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The ESCASA algorithm for analytical estimation of proton positions from coarsegrained geometry developed in our recent work has been implemented in modeling protein structures with the highly coarse-grained UNRES model of polypeptide chains (two sites per residue) and nuclear magnetic resonance (NMR) data. A penalty function with the shape of intersecting gorges was applied to treat ambiguous distance restraints, which automatically selects consistent restraints. Hamiltonian replica exchange molecular dynamics was used to carry out the conformational search. The method was tested with both unambiguous and ambiguous restraints producing good-quality models with GDT_TS from 7.4 units higher to 14.4 units lower than those obtained with the CYANA or MELD software for protein-structure determination from NMR data at the all-atom resolution. The method can thus be applied in modeling the structures of flexible proteins, for which extensive conformational search enabled by coarse-graining is more important than high modeling accuracy.

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Optimization of parallel implementation ofUNRESpackage for coarse‐grained simulations to treat large proteins

et al. 2022

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We report major algorithmic improvements of the UNRES package for physics-based coarse-grained simulations of proteins. These include (i) introduction of interaction lists to optimize computations, (ii) transforming the inertia matrix to a pentadiagonal form to reduce computing and memory requirements, (iii) removing explicit angles and dihedral angles from energy expressions and recoding the most time-consuming energy/force terms to minimize the number of operations and to improve numerical stability, (iv) using OpenMP to parallelize those sections of the code for which distributed-memory parallelization involves unfavorable computing/communication time ratio, and (v) careful memory management to minimize simultaneous access of distant memory sections. The new code enables us to run molecular dynamics simulations of protein systems with size exceeding 100,000 amino-acid residues, reaching over 1 ns/day (1 μs/day in all-atom timescale) with 24 cores for proteins of this size.

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Modeling protein structures with the coarse-grained UNRES force field in the CASP14 experiment

Cited by 20 publications

References 58 publications

Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model

Prediction of Aggregation of Biologically-Active Peptides with the UNRES Coarse-Grained Model

A coarse‐grained approach toNMR‐data‐assisted modeling of protein structures

Optimization of parallel implementation ofUNRESpackage for coarse‐grained simulations to treat large proteins

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