Prediction of Side Chain Orientations in Proteins by Statistical Machine Learning Methods

Abstract

We develop ways to predict the side chain orientations of residues within a protein structure by using several different statistical machine learning methods. Here side chain orientation of a given residue i is measured by an angle Ω_i between the vector pointing from the center of the protein structure to the C^α _i atom and the vector pointing from the C^α _i atom to the center of its side chain atoms. To predict the Ω_i angles, we construct statistical models by using several different methods such as general linear regression, a regression tree and bagging, a neural network, and a support vector machine. The root mean square errors for the different models range only from 36.67 to 37.60 degrees and the correlation coefficients are all between 30% and 34%. The performances of different models in the test set are, thus, quite similar, and show the relative predictive power of these models to be significant in comparison with random side chain orientations.     

Organ-specific fuel rewiring in acute and chronic hypoxia redistributes glucose and fatty acid metabolism

1. Download : Download high-res image (182KB)
2. Download : Download full-size image

     

Abundance,survival, and annual rate of change of Cuvier's beaked whales (Ziphius cavirostris) on a Navy sonar range

Bayesian mark-recapture estimates of survival, abundance, and trend are reported for Cuvier's beaked whales (Ziphius cavirostris) using a Navy training range off southern California. The deep-diving beaked whale family is exceptionally vulnerable to mid-frequency active sonar (MFAS), which has been implicated in mass strandings and altered foraging behavior. Extremely low sighting probabilities impede studies of population-level impacts of MFAS on beaked whales. The San Nicolas Basin hosts a Navy training range subject to frequent MFAS use and attracts high densities of Z. cavirostris. An 11-year (2007–2018) photo-identification program leveraged automated acoustic detection and location capabilities on the range's 1,800-km² hydrophone array to enhance capture probability. Estimated population parameters for Z. cavirostris using the range included mean (90% credibility intervals) apparent annual survival of 0.950 (0.899–0.986), annual number of individuals as 121 (71–219), and annual rate of change of −0.8% (−5.6%–4.1%). Simulations show the probability of detecting abundance changes is currently low, but can be greatly improved through continued monitoring and increased effort. Complementary data collection on habitat use and demographic rates in San Nicolas and surrounding basins is also essential to relating direct effects of MFAS use to changes in vital rates and broader population outcomes.     

Freshwater mussel conservation: A global horizon scan of emerging threats and opportunities

We identified 14 emerging and poorly understood threats and opportunities for addressing the global conservation of freshwater mussels over the next decade. A panel of 17 researchers and stakeholders from six continents submitted a total of 56 topics that were ranked and prioritized using a consensus-building Delphi technique. Our 14 priority topics fell into five broad themes (autecology, population dynamics, global stressors, global diversity, and ecosystem services) and included understanding diets throughout mussel life history; identifying the drivers of population declines; defining metrics for quantifying mussel health; assessing the role of predators, parasites, and disease; informed guidance on the risks and opportunities for captive breeding and translocations; the loss of mussel–fish co-evolutionary relationships; assessing the effects of increasing surface water changes; understanding the effects of sand and aggregate mining; understanding the effects of drug pollution and other emerging contaminants such as nanomaterials; appreciating the threats and opportunities arising from river restoration; conserving understudied hotspots by building local capacity through the principles of decolonization; identifying appropriate taxonomic units for conservation; improved quantification of the ecosystem services provided by mussels; and understanding how many mussels are enough to provide these services. Solutions for addressing the topics ranged from ecological studies to technological advances and socio-political engagement. Prioritization of our topics can help to drive a proactive approach to the conservation of this declining group which provides a multitude of important ecosystem services.     

Solid support-dependent alkylation of tryptophan residues in SPPS using a 2-methoxybenzyl alcohol-based linker

Summary Several side reactions can be encountered in the synthesis of Trp-containing peptides, due to molecular species originating from side chain-protecting groups or from the linker during acidolytic cleavage of the peptide from the resin. The linker can be the source of both alkylation in solution of the indole moiety of the tryptophan side chain and permanent readdition of the cleaved peptide to the resin. We report that both these reactions occur at a high level during the synthesis of Trp-containing peptides on a PEG-PS resin containing a 2-methoxybenzyl alcohol-based linker, in spite of the presence of suitable scavengers in the TFA-based cleavage mixture. Both side reactions are efficiently prevented by the use of a protected analogue of tryptophan, namely N^im-Boc-Trp, previously reported for the synthesis of peptides containing tryptophan and arginine residues.     

CT scan reconstruction of the palate region of Latimeria chalumnae

Synopsis The palate of Latimeria chalumnae is described based mainly on three-dimensional CT scan reconstruction. It is compared with that of other osteichthyans. The palate of L. chalumnae compares best with that of rhipidistians; it is more advanced than that of actinopterygians in having fewer bones. This tendency toward bone reduction in the palate is even more pronounced in dipnoans. The interpretation of features of the Early Devonian genus Diabolepis determines if authors consider dipnoans or actinistians more closely related to tetrapods. Both groups are only distant relatives of tetrapods.