Dr. Lance Westerhoff will be presenting a poster concerning the Company’s recent work in Protein/Protein QM-based interaction profiling at Chemical Computing Group’s North American User Group Meeting in Montreal, Quabec.

Title: Computational alanine scanning with linear scaling semi-empirical quantum mechanical methods within MOE

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 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. 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.

This method has since been implemented within the interface between MOE and QuantumBio’s protein-QM toolkit (QBLib). With this integration, not only can the system be prepared, tested, and executed within the familiar MOE interface, but the QM-based interactions between two proteins can now be visualized in order to gain maximum insight.

Reference: Diller, D.J., C. Humblet, X. Zhang, and L.M. Westerhoff, Computational alanine scanning with linear scaling semiempirical quantum mechanical methods. Proteins, 2010. 78(10): p. 2329-37 (DOI: 10.1002/prot.22745).