Next Article in Journal
Pheophorbide a: State of the Art
Previous Article in Journal
Bioactive Molecules from Mangrove Streptomyces qinglanensis 172205
Open AccessArticle

Graph-Directed Approach for Downselecting Toxins for Experimental Structure Determination

1
Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
2
Center for Nonlinear Studies, Los Alamos National Laboratory, Los Alamos, NM 87545, USA
*
Author to whom correspondence should be addressed.
Current address: Pebble Labs Inc., Los Alamos, NM 87544, USA.
Mar. Drugs 2020, 18(5), 256; https://doi.org/10.3390/md18050256
Received: 6 March 2020 / Revised: 24 April 2020 / Accepted: 9 May 2020 / Published: 14 May 2020
(This article belongs to the Special Issue Virtual Screening of Marine Natural Products)
Conotoxins are short, cysteine-rich peptides of great interest as novel therapeutic leads and of great concern as lethal biological agents due to their high affinity and specificity for various receptors involved in neuromuscular transmission. Currently, of the approximately 6000 known conotoxin sequences, only about 3% have associated structural characterization, which leads to a bottleneck in rapid high-throughput screening (HTS) for identification of potential leads or threats. In this work, we combine a graph-based approach with homology modeling to expand the library of conotoxin structures and to identify those conotoxin sequences that are of the greatest value for experimental structural characterization. The latter would allow for the rapid expansion of the known structural space for generating high quality template-based models. Our approach generalizes to other evolutionarily-related, short, cysteine-rich venoms of interest. Overall, we present and validate an approach for venom structure modeling and experimental guidance and employ it to produce a 290%-larger library of approximate conotoxin structures for HTS. We also provide a set of ranked conotoxin sequences for experimental structure determination to further expand this library. View Full-Text
Keywords: conotoxins; protein structure determination; homology modeling; network analysis conotoxins; protein structure determination; homology modeling; network analysis
Show Figures

Figure 1

MDPI and ACS Style

Mansbach, R.A.; Chakraborty, S.; Travers, T.; Gnanakaran, S. Graph-Directed Approach for Downselecting Toxins for Experimental Structure Determination. Mar. Drugs 2020, 18, 256.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop