Publication: Computational alanine scanning with linear scaling semi-empirical quantum mechanical methods
April 09, 2010
Abstract: Alanine scanning is a powerful experimental tool for understanding the key
interactions in protein-protein interfaces. Linear scaling semi-empirical
quantum mechanical calculations are now sufficiently fast and robust to allow
meaningful calculations on large systems such as proteins, RNA and DNA. In
particular, they have proven useful in understanding protein-ligand
interactions. Here we ask the question: can these linear scaling quantum
mechanical methods developed for protein-ligand scoring be useful for
computational alanine scanning? To answer this question, we assembled 15
protein-protein complexes with available crystal structures and sufficient
alanine scanning data. In all, the data set contains Gs for 400 single point
alanine mutations of these 15 complexes. We show that with only one adjusted
parameter the quantum mechanics based methods out perform both buried accessible
surface area and a potential of mean force and compare favorably to a variety of
published empirical methods. Finally, we closely examined the outliers in the
data set and discuss some of the challenges that arise from this examination.
Authors: David J. Diller, Christine Humblet, Xiaohua Zhang, Lance M. Westerhoff
Reference: Proteins: Structure, Function, and Bioinformatics, 2010, ASAP. (see
link for full paper).