An energy-based conformer library for side chain optimization: improved prediction and adjustable sampling

Proteins
Sabareesh Subramaniam, Alessandro Senes

Abstract

Side chain optimization is a fundamental component of protein modeling applications such as docking, structural prediction, and design. In these applications side chain flexibility is often provided by rotamer or conformer libraries, which are collections of representative side chain conformations. Here we demonstrate that the sampling provided by the library can be substantially improved by adding an energetic criterion to its creation. The result of the new procedure is the Energy-Based library, a conformer library selected according to the propensity of its elements to fit energetically into natural protein environments. The new library performs outstandingly well in side chain optimization, producing structures with significantly lower energies and resulting in improved side chain conformation prediction. In addition, because the library was created as an ordered list, its size can be adjusted to any desired level. This feature provides unprecedented versatility in tuning sampling. It allows to precisely balance the number of conformers required by each amino acid type, equalizing their chances to fit into structural environments. It also allows to scale the amount of sampling to the specific requirement of any given side o...Continue Reading

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Citations

Feb 27, 2014·Proceedings of the National Academy of Sciences of the United States of America·Benjamin K MuellerAlessandro Senes
Sep 10, 2014·Acta Crystallographica. Section D, Biological Crystallography·Ryan McGreevyKlaus Schulten
Jan 1, 2015·BMC Structural Biology·Xubiao PengAntti J Niemi
Oct 14, 2017·Journal of the American Chemical Society·Samantha M AndersonAlessandro Senes
Mar 26, 2013·Biochemistry·Loren M LaPointeAlessandro Senes
Sep 13, 2014·Journal of the American Chemical Society·Ambalika S KhadriaAlessandro Senes

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