Search bioRxiv⌕ Search

Biology subjects

Martin, J. W.

Publications and source records attributed to Martin, J. W..

2 recordsLinked to original sources
bioRxiv2018

OSPREY 3.0: Open-Source Protein Redesign for You, with Powerful New Features

We present O_SCPCAPOSPREYC_SCPCAP 3.0, a new and greatly improved release of the O_SCPLOWOSPREYC_SCPLOW protein design software. O_SCPLOWOSPREYC_SCPLOW 3.0 features a convenient new Python interface, which greatly improves its ease of use. It is over two orders of magnitude faster than previous versions of O_SCPLOWOSPREYC_SCPLOW when running the same algorithms on the same hardware. Moreover, O_SCPLOWOSPREYC_SCPLOW 3.0 includes several new algorithms, which introduce substantial speedups as well as improved biophysical modeling. It also includes GPU support, which provides an additional speedup of over an order of magnitude. Like previous versions of O_SCPLOWOSPREYC_SCPLOWO_SCPCAP, C_SCPCAPO_SCPLOWOSPREYC_SCPLOW 3.0 offers a unique package of advantages over other design software, including provable design algorithms that account for continuous flexibility during design and model conformational entropy. Finally, we show here empirically that O_SCPLOWOSPREYC_SCPLOW 3.0 accurately predicts the effect of mutations on protein-protein binding. O_SCPLOWOSPREYC_SCPLOW 3.0 is available at http://www.cs.duke.edu/donaldlab/osprey.php as free and open-source software.\n\nO_TEXTBOX\n\nWe present the third major release of the OSPREY protein design software, along with comparisons to experimental data that confirm its ability to optimize protein mutants for desired functions. osprey 3.0 has significant efficiency, ease-of-use, and algorithmic improvements over previous versions, including GPU acceleration and a new Python interface.\n\nC_TEXTBOX\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=162 SRC=\"FIGDIR/small/306324v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (54K):\norg.highwire.dtl.DTLVardef@f08b0dorg.highwire.dtl.DTLVardef@393b61org.highwire.dtl.DTLVardef@16997ddorg.highwire.dtl.DTLVardef@1713405_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗
bioRxiv2017

Continuous interdomain orientation distributions reveal components of binding thermodynamics

1The flexibility of biological macromolecules is an important structural determinant of function. Unfortunately, the correlations between different motional modes are poorly captured by discrete ensemble representations. Here, we present new ways to both represent and visualize correlated interdomain motions. Interdomain motions are determined directly from residual dipolar couplings (RDCs), represented as a continuous conformational distribution, and visualized using the disk-on-sphere (DoS) representation. Using the DoS representation, features of interdomain motions, including correlations, are intuitively visualized. The representation works especially well for multidomain systems with broad conformational distributions. This analysis also can be extended to multiple probability density modes, using a Bingham mixture model. We use this new paradigm to study the interdomain motions of staphylococcal protein A, which is a key virulence factor contributing to the pathogenicity of S. aureus. We capture the smooth transitions between important states and demonstrate the utility of continuous distribution functions for computing components of binding thermodynamics. Such insights allow the dissection the dynamic structural components of functionally important intermolecular interactions.

biophysics↗