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Updated: Aug 25, 2025

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
Published on: July 25, 2013
Exploiting Sequence-Dependent Rotamer Information in Global Optimization of Proteins
1Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, United Kingdom.
Abstract:
Rotamers, namely amino acid side chain conformations common to many different peptides, can be compiled into libraries. These rotamer libraries are used in protein modeling, where the limited conformational space occupied by amino acid side chains is exploited. Here, we construct a sequence-dependent rotamer library from simulations of all possible tripeptides, which provides rotameric states dependent on adjacent amino acids. We observe significant sensitivity of rotamer populations to sequence and find that the library is successful in locating side chain conformations present in crystal structures. The library is designed for applications with basin-hopping global optimization, where we use it to propose moves in conformational space. The addition of rotamer moves significantly increases the efficiency of protein structure prediction within this framework, and we determine parameters to optimize efficiency.
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