De Novo Membrane Protein Structure Prediction

2014 ◽  
pp. 331-350 ◽  
Author(s):  
Timothy Nugent
Keyword(s):  
Protein Structure ◽  
Membrane Protein ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
De Novo ◽  
Membrane Protein Structure

scholarly journals Protein structure prediction and design in a biologically-realistic implicit membrane

2019 ◽  
Author(s):  
Rebecca F. Alford ◽  
Patrick J. Fleming ◽  
Karen G. Fleming ◽  
Jeffrey J. Gray
Keyword(s):  
Protein Structure ◽  
Amino Acid ◽  
Membrane Proteins ◽  
Membrane Protein ◽  
Protein Structure Prediction ◽  
Protein Design ◽  
Structure Prediction ◽  
De Novo ◽  
Computational Design ◽  
Amino Acid Distribution

ABSTRACTProtein design is a powerful tool for elucidating mechanisms of function and engineering new therapeutics and nanotechnologies. While soluble protein design has advanced, membrane protein design remains challenging due to difficulties in modeling the lipid bilayer. In this work, we developed an implicit approach that captures the anisotropic structure, shape of water-filled pores, and nanoscale dimensions of membranes with different lipid compositions. The model improves performance in computational bench-marks against experimental targets including prediction of protein orientations in the bilayer, ΔΔG calculations, native structure dis-crimination, and native sequence recovery. When applied to de novo protein design, this approach designs sequences with an amino acid distribution near the native amino acid distribution in membrane proteins, overcoming a critical flaw in previous membrane models that were prone to generating leucine-rich designs. Further, the proteins designed in the new membrane model exhibit native-like features including interfacial aromatic side chains, hydrophobic lengths compatible with bilayer thickness, and polar pores. Our method advances high-resolution membrane protein structure prediction and design toward tackling key biological questions and engineering challenges.Significance StatementMembrane proteins participate in many life processes including transport, signaling, and catalysis. They constitute over 30% of all proteins and are targets for over 60% of pharmaceuticals. Computational design tools for membrane proteins will transform the interrogation of basic science questions such as membrane protein thermodynamics and the pipeline for engineering new therapeutics and nanotechnologies. Existing tools are either too expensive to compute or rely on manual design strategies. In this work, we developed a fast and accurate method for membrane protein design. The tool is available to the public and will accelerate the experimental design pipeline for membrane proteins.

scholarly journals Genome-wide Membrane Protein Structure Prediction

2013 ◽  
Vol 14 (5) ◽  
pp. 324-329 ◽  
Author(s):  
Stefano Piccoli ◽  
Eda Suku ◽  
Marianna Garonzi ◽  
Alejandro Giorgetti
Keyword(s):  
Protein Structure ◽  
Membrane Protein ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Membrane Protein Structure ◽  
Genome Wide

scholarly journals Optimal Mutation Sites for PRE Data Collection and Membrane Protein Structure Prediction

Structure ◽  
2011 ◽  
Vol 19 (4) ◽  
pp. 484-495 ◽  
Author(s):  
Huiling Chen ◽  
Fei Ji ◽  
Victor Olman ◽  
Charles K. Mobley ◽  
Yizhou Liu ◽  
...  
Keyword(s):  
Protein Structure ◽  
Data Collection ◽  
Membrane Protein ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Membrane Protein Structure

scholarly journals Multipass membrane protein structure prediction using Rosetta

2005 ◽  
Vol 62 (4) ◽  
pp. 1010-1025 ◽  
Author(s):  
Vladimir Yarov-Yarovoy ◽  
Jack Schonbrun ◽  
David Baker
Keyword(s):  
Protein Structure ◽  
Membrane Protein ◽  
Protein Structure Prediction ◽  
Structure Prediction ◽  
Membrane Protein Structure
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