New Dynamic Rotamer Libraries: Data-Driven Analysis of Side-Chain Conformational Propensities

• Published in: Structure (London) Vol. 24; no. 1; pp. 187 - 199
• Main Authors: Towse, Clare-Louise, Rysavy, Steven J., Vulovic, Ivan M., Daggett, Valerie
• Format: Journal Article
• Language: English
• Published: United States Elsevier Ltd 05.01.2016; Elsevier
• Subjects: Animals; Humans; Isomerism; Molecular Dynamics Simulation; Peptide Library; Protein Conformation; Software; Ubiquitins - chemistry
• ISSN: 0969-2126; 1878-4186
• DOI: 10.1016/j.str.2015.10.017

Most rotamer libraries are generated from subsets of the PDB and do not fully represent the conformational scope of protein side chains. Previous attempts to rectify this sparse coverage of conformational space have involved application of weighting and smoothing functions. We resolve these limitations by using physics-based molecular dynamics simulations to determine more accurate frequencies of rotameric states. This work forms part of our Dynameomics initiative and uses a set of 807 proteins selected to represent 97% of known autonomous protein folds, thereby eliminating the bias toward common topologies found within the PDB. Our Dynameomics derived rotamer libraries encompass 4.8 × 109 rotamers, sampled from at least 51,000 occurrences of each of 93,642 residues. Here, we provide a backbone-dependent rotamer library, based on secondary structure ϕ/ψ regions, and an update to our 2011 backbone-independent library that addresses the doubling of our dataset since its original publication. [Display omitted] •Improving rotamer libraries aids structure design, prediction, and modeling•Dynameomics is the simulation of solvated structures representing 97% of fold space•Dynamic rotamer libraries were created from the Boltzmann sampling of side chains•Including dynamics showed rare rotamers to be dominant in some areas of ϕ/ψ space Accurate rotamer libraries are necessary to improve the modeling and prediction of protein structures. Towse et al. present a new set of rotamer libraries constructed from 4.8 × 109 side-chain samples obtained through the simulation of 807 solvated structures at ambient temperature.