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Updated: Jan 10, 2026

Atomic Scale Structural Studies of Macromolecular Assemblies by Solid-state Nuclear Magnetic Resonance Spectroscopy
Published on: September 17, 2017
Implementation of Replica-Averaged Restraints from Nuclear Magnetic Resonance Measurement with UNRES Coarse Grained
Leonid Shirkov1,2, Cezary Czaplewski1, Adam Liwo1
1Faculty of Chemistry, University of Gdańsk, Fahrenheit Union of Universities, Wita Stwosza 63, 80-308 Gdańsk, Poland.
Abstract:
We report the implementation of replica-averaged molecular dynamics in the UNRES coarse-grained model of polypeptide chains, with application to the restraints determined by nuclear magnetic resonance. The analytical ESCASA algorithm is used to estimate interproton distances from coarse-grained geometry. With synthetic restraints derived from two selected conformations of the L129-L153 loop of the Slr1183 protein from Synechocystis sp. (2KW5), the replica-averaged extension of UNRES retrieved the ensemble of conformations close to the parent structures, with residual content of those not similar to any of them, and comparable populations of both families. Tests with a small putatively multistate protein (PDB: 2LWA) and two proteins with disordered regions (2KW5 and 2KZN, respectively) run in multiplexed temperature replica exchange mode with replica averaging resulted in conformational ensembles that had fewer distance-restraint violations than those deposited in the Protein Data Bank. The ensembles obtained with replica averaging also had fewer distance-restraint violations than those obtained in our previous work, in which time-averaged restraints were implemented. The upgraded UNRES can be used in data-assisted simulations of multistate and intrinsically-disordered proteins and proteins with intrinsically disordered regions.
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