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11:36
A Protocol for Functional Assessment of Whole-Protein Saturation Mutagenesis Libraries Utilizing High-Throughput Sequencing
Published on: July 3, 2016
Fast side chain replacement in proteins using a coarse-grained approach for evaluating the effects of mutation during
Johan A Grahnen1, Jan Kubelka, David A Liberles
1Department of Molecular Biology, University of Wyoming, Laramie, WY 82071, USA. jgrahnen@uwyo.edu
Journal of Molecular Evolution
|July 30, 2011
Summary
A new coarse-grained method accelerates structural evaluation of protein substitutions by sevenfold, maintaining accuracy for high-throughput bioinformatics and evolutionary studies.
Area of Science:
- Bioinformatics
- Structural Biology
- Computational Biology
Background:
- High-throughput structural genomic and evolutionary bioinformatics require fast methods for evaluating structural substitutions.
- Current all-atom approaches are computationally intensive, limiting their applicability in large-scale studies.
Purpose of the Study:
- To present a novel coarse-grained method for positioning substituted side chains.
- To improve the speed and efficiency of structural substitution evaluation in proteins.
Main Methods:
- Development and application of a coarse-grained computational approach for side chain positioning.
- Comparison with existing all-atom methods for speed and accuracy.
- Implementation in a forward simulation of SH2 domain evolution.
Main Results:
- Achieved at least a sevenfold speed-up for single-residue replacements compared to all-atom methods.
- Maintained a small median RMSD (in coarse-grained space) and similar prediction accuracy for point mutants.
- Demonstrated biologically realistic side chain angles and predictable run times.
Conclusions:
- The coarse-grained method offers a significant speed advantage for high-throughput protein structural evolution studies.
- The approach maintains accuracy comparable to all-atom methods, making it suitable for large-scale bioinformatics.
- The freely available SARA software facilitates its application in evolutionary and structural genomic research.
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