SWISS-MODEL: homology modelling of protein structures and complexes.

Andrew Waterhouse,Tjaart A P De Beer,Florian T Heer,Christine Rempfer,Stefan Bienert,Rosalba Lepore,Martino Bertoni,Torsten Schwede,Gabriel Studer,Lorenza Bordoli,Gerardo Tauriello,Rafal Gumienny

doi:10.1093/nar/gky427

Andrew Waterhouse, Tjaart A P De Beer + Show 10 more

Open Access

https://doi.org/10.1093/nar/gky427

Copy DOI

Abstract

Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org.

Highlights

Three-dimensional structures of proteins provide valuable insights into their function on a molecular level and inform a broad spectrum of applications in life science research
Computational structural modelling methods have established themselves as a valuable complement to experimen
With the new version of SWISS-MODEL presented here, we aimed at extending the scope of automated homology modelling to address the modelling of protein assemblies by efficiently using the information on quaternary structures available in the Protein Data Bank (PDB)

Summary

Introduction

Three-dimensional structures of proteins provide valuable insights into their function on a molecular level and inform a broad spectrum of applications in life science research. A detailed description of their interactions and the overall quaternary structure is essential for a comprehensive understanding of biological systems, how protein complexes and networks operate and how we can modulate them [1,2]. Still, compared to highthroughput methods for screening protein-protein interactions (i.e. yeast two-hybrid, affinity purification, phagedisplay etc.), the rate at which novel complex structures are determined experimentally is considerably lower. This uneven growth calls for computational methods to fill the gap

Methods

Results

Conclusion