DROIDS 3.0-Detecting Genetic and Drug Class Variant Impact on Conserved Protein Binding Dynamics.

The application of statistical methods to comparatively framed questions about the molecular dynamics (MD) of proteins can potentially enable investigations of biomolecular function beyond the current sequence and structural methods in bioinformatics. However, the chaotic behavior in single MD trajectories requires statistical inference that is derived from large ensembles of simulations representing the comparative functional states of a protein under investigation. Meaningful interpretation of such complex forms of big data poses serious challenges to users of MD. Here, we announce Detecting Relative Outlier Impacts from Molecular Dynamic Simulation (DROIDS) 3.0, a method and software package for comparative protein dynamics that includes maxDemon 1.0, a multimethod machine learning application that trains on large ensemble comparisons of concerted protein motions in opposing functional states generated by DROIDS and deploys learned classifications of these states onto newly generated MD simulations. Local canonical correlations in learning patterns generated from independent, yet identically prepared, MD validation runs are used to identify regions of functionally conserved protein dynamics. The subsequent impacts of genetic and/or drug class variants on conserved dynamics can also be analyzed by deploying the classifiers on variant MD simulations and quantifying how often these altered protein systems display opposing functional states. Here, we present several case studies of complex changes in functional protein dynamics caused by temperature, genetic mutation, and binding interactions with nucleic acids and small molecules. We demonstrate that our machine learning algorithm can properly identify regions of functionally conserved dynamics in ubiquitin and TATA-binding protein (TBP). We quantify the impact of genetic variation in TBP and drug class variation targeting the ATP-binding region of Hsp90 on conserved dynamics. We identify regions of conserved dynamics in Hsp90 that connect the ATP binding pocket to other functional regions. We also demonstrate that dynamic impacts of various Hsp90 inhibitors rank accordingly with how closely they mimic natural ATP binding.

Relative expression analysis of light-harvesting genes in the freshwater alga Lympha mucosa (Batrachospermales, Rhodophyta).

Members of the freshwater red algal order Batrachospermales are often described as shade-adapted. Nevertheless, recent ecophysiological studies have demonstrated species-level differences in acclimation to a range of irradiances. Lympha mucosa occurs in open and shaded portions of temperate streams and is abundant during summer months, suggesting it tolerates high and low irradiances. Specimens of L. mucosa were collected from open (sun-acclimated) or shaded (shade-acclimated) sites and exposed to low (<20 µmol photons · m-2 · s-1 ) or high (220 µmol photon · m-2 · s-1 ) light for 72 h to examine mechanisms of photoacclimation at the transcriptional level. High-throughput sequence data were used to design specific primers for genes involved with light harvesting and these were quantified with qPCR. The greatest significant difference in transcript abundances was observed in the psaA gene (Photosystem I P700 apoprotein), and site-type had an effect on these responses. Shade-acclimated thalli were 22-fold down-regulated at high light, whereas sun-acclimated thalli were only 5-fold down-regulated. Another gene involved with Photosystem I (petF ferredoxin) was down-regulated at high light, but only individuals from the shaded site were significantly different (4-fold). In thalli from both sites, cpeA (Phycoerythrin alpha chain) was down-regulated at high light. Although not statistically significant, patterns consistent with previous physiological and transcriptomic studies were uncovered, namely the inverse response of transcriptional activity in genes that encode phycobiliproteins. In support of previous ecophysiological studies of freshwater red algae, these data indicate significant transcriptional changes involving Photosystem I and phycobiliprotein synthesis are required to tolerate and grow at various irradiances.

Ottia meiospora (Ottiaceae, Rhodophyta), a new genus and family endophytic within the thallus of Nothocladus (Batrachospermales, Rhodophyta).

A new genus, Ottia, and family, Ottiaceae, are proposed within the Acrochaetiales to accommodate the uniseriate red algal endophyte of batrachspermalean taxa previously named Balbiania meiospora. Prior to this study, Balbiania investiens was transferred to its own family and order (Balbianiales) based on comparative DNA sequence data and a distinctive reproductive morphology. However, the second species described in this genus, B. meiospora, continued to be treated as a species of Audouinella (A. meiospora) pending further investigation. Phylogenetic analyses of sequence data confirmed only a distant relationship between the two endophytes, and a closer alliance of B. meiospora to Acrochaetiales. The data also showed that Ottia meiospora was the deepest diverging lineage in the Acrochaetiales, sister to all of the currently recognized genera and families. In this study, we review the classification of what we now call O. meiospora - reported from Australia, New Zealand and Brazil - based on sequence and morphological data. Morphological observations provided little clarity around the reproductive morphology or the life cycle of this endophyte of Nothocladus s. lat. found commonly in mainland Australia but, to date, less so in New Zealand.

PCR fishing for red endophytes in British Columbia Kallymeniaceae (Gigartinales, Florideophyceae) uncovers the species-rich Kallymenicola gen. nov. (Palmariales, Nemaliophycidae).

Unexpected contaminants uncovered during routine COI-5P DNA barcoding of British Columbia Kallymeniaceae indicated the presence of a novel lineage allied to the family Meiodiscaceae, Palmariales. Available rbcL data for species of this family were used to design specific primers to screen for the presence of the meiodiscacean species in 534 kallymeniacean specimens primarily from British Columbia, Canada. Ultimately, 43 positive PCR products representing six diverse genetic groups from nine host species were uncovered; three are described here in the new genus Kallymenicola gen. nov., viz., K. invisiblis sp. nov., K penetrans sp. nov., and K superficialis sp. nov. Although genetic groups loosely displayed evidence of host specificity and cospeciation, examples of host switching with interesting biogeographical patterns were also documented.

Complete mitochondrial genome of the freshwater red alga Lympha mucosa (Rhodophyta).

We present the complete mitochondrial genome of a newly described freshwater red alga Lympha mucosa. The genome was sequenced using the Illumina MiSeq platform. The circular mitochondrial genome is 25,191 bp, contains 46 genes (24 CDS, 20 tRNA, and 2 rRNA), and has an overall GC content of 27.5%. Phylogenetic analyses of the cox1 gene show the placement of Lympha mucosa within the strictly freshwater order Batrachospermales. The four mitochondrial genomes within the subclass Nemaliophycidae sequenced to date are highly conserved in terms of genome size, gene content, and gene synteny.