Using quantum mechanics to improve estimates of amino acid side chain rotamer energies

Amino acid side chains adopt a discrete set of favorable conformations typically referred to as rotamers. The relative energies of rotamers partially determine which side chain conformations are more often observed in protein structures and accurate estimates of these energies are important for predicting protein structure and designing new proteins. Protein modelers typically calculate side chain rotamer energies by using molecular mechanics (MM) potentials or by converting rotamer probabilities from the protein database (PDB) into relative free energies. One limitation of the knowledge-based energies is that rotamer preferences observed in the PDB can reflect internal side chain energies as well as longer-range interactions with the rest of the protein. Here, we test an alternative approach for calculating rotamer energies. We use three different quantum mechanics (QM) methods (second order Moller-Plesset (MP2), density functional theory (DFT) energy calculation using the B3LYP functional, and Hartree-Fock) to calculate the energy of amino acid rotamers in a dipeptide model system, and then use these pre-calculated values in side chain placement simulations. Energies were calculated for over 35,000 different conformations of leucine, isoleucine and valine dipeptides with backbone torsion angles from the helical and strand regions of the Ramachandran plot. In a subset of cases these energies differ significantly from those calculated with standard molecular mechanics potentials or those derived from PDB statistics. We find that in these cases the energies from the QM methods result in more accurate placement of amino acid side chains in structure prediction tests

Serverification of Molecular Modeling Applications: the Rosetta Online Server that Includes Everyone (ROSIE)

The Rosetta molecular modeling software package provides experimentally tested and rapidly evolving tools for the 3D structure prediction and high-resolution design of proteins, nucleic acids, and a growing number of non-natural polymers. Despite its free availability to academic users and improving documentation, use of Rosetta has largely remained confined to developers and their immediate collaborators due to the code's difficulty of use, the requirement for large computational resources, and the unavailability of servers for most of the Rosetta applications. Here, we present a unified web framework for Rosetta applications called ROSIE (Rosetta Online Server that Includes Everyone). ROSIE provides (a) a common user interface for Rosetta protocols, (b) a stable application programming interface for developers to add additional protocols, (c) a flexible back-end to allow leveraging of computer cluster resources shared by RosettaCommons member institutions, and (d) centralized administration by the RosettaCommons to ensure continuous maintenance. This paper describes the ROSIE server infrastructure, a step-by-step 'serverification' protocol for use by Rosetta developers, and the deployment of the first nine ROSIE applications by six separate developer teams: Docking, RNA de novo, ERRASER, Antibody, Sequence Tolerance, Supercharge, Beta peptide design, NCBB design, and VIP redesign. As illustrated by the number and diversity of these applications, ROSIE offers a general and speedy paradigm for serverification of Rosetta applications that incurs negligible cost to developers and lowers barriers to Rosetta use for the broader biological community. ROSIE is available at http://rosie.rosettacommons.org

Avian Use of Perennial Biomass Feedstocks as Post-Breeding and Migratory Stopover Habitat

Increased production of biomass crops in North America will require new agricultural land, intensify the cultivation of land already under production and introduce new types of biomass crops. Assessing the potential biodiversity impacts of novel agricultural systems is fundamental to the maintenance of biodiversity in agricultural landscapes, yet the consequences of expanded biomass production remain unclear. We evaluate the ability of two candidate second generation biomass feedstocks (switchgrass, Panicum virgatum, and mixed-grass prairie) not currently managed as crops to act as post-breeding and fall migratory stopover habitat for birds. In total, we detected 41 bird species, including grassland specialists and species of state and national conservation concern (e.g. Henslow's Sparrow, Ammodramus henslowii). Avian species richness was generally comparable in switchgrass and prairie and increased with patch size in both patch types. Grassland specialists were less abundant and less likely to occur in patches within highly forested landscapes and were more common and likely to occur in larger patches, indicating that this group is also area-sensitive outside of the breeding season. Variation in the biomass and richness of arthropod food within patches was generally unrelated to richness and abundance metrics. Total bird abundance and that of grassland specialists was higher in patches with greater vegetation structural heterogeneity. Collectively, we find that perennial biomass feedstocks have potential to provide post-breeding and migratory stopover habitat for birds, but that the placement and management of crops will be critical factors in determining their suitability for species of conservation concern. Industrialization of cellulosic bioenergy production that results in reduced crop structural heterogeneity is likely to dramatically reduce the suitability of perennial biomass crops for birds

Unravelling the complexity of domestication:A case study using morphometrics and ancient DNA analyses of archaeological pigs from Romania

Funding statement. This work was supported by the Natural Environment Research Council (NE/F003382/1) and the Leverhulme Trust (F/00 128/AX) Acknowledgements. Archaeozoological analyses conducted by A. Ba˘la˘s¸escu were supported by three grants from the Romanian National Authority for Scientific Research, CNCS UEFISCDI (PN-II-RU-TE-20113-0146, PN-II-ID-PCE-2011-3-0982 and PN-IIID-PCE-2011-3-1015). We thank the archeologists Ca˘ta˘lin Bem, Alexandru Dragoman, Valentin Dumitras¸cu, Laura Dietrich, Raluca Koga˘lniceanu, Cristian Micu, Sta˘nica Pandrea, Valentin Parnic, George Trohani, Valentina Voinea for the material they generously provided. We thank the many institutions and individuals that provided sample material and access to collections, especially the curators of the Museum fu¨r Naturkunde, Berlin; Muse´um National d’Histoire Naturelle, Paris; Muse´um d’Histoire Naturelle, Gene`ve; Museum fu¨r Haustierkunde, Halle; National Museum of Natural History, Washington; The Field Museum, Chicago and The American Museum of Natural History, New York; The Naturhistorisches Museum, BernPeer reviewedPublisher PD

A História da Alimentação: balizas historiográficas

Os M. pretenderam traçar um quadro da História da Alimentação, não como um novo ramo epistemológico da disciplina, mas como um campo em desenvolvimento de práticas e atividades especializadas, incluindo pesquisa, formação, publicações, associações, encontros acadêmicos, etc. Um breve relato das condições em que tal campo se assentou faz-se preceder de um panorama dos estudos de alimentação e temas correia tos, em geral, segundo cinco abardagens Ia biológica, a econômica, a social, a cultural e a filosófica!, assim como da identificação das contribuições mais relevantes da Antropologia, Arqueologia, Sociologia e Geografia. A fim de comentar a multiforme e volumosa bibliografia histórica, foi ela organizada segundo critérios morfológicos. A seguir, alguns tópicos importantes mereceram tratamento à parte: a fome, o alimento e o domínio religioso, as descobertas européias e a difusão mundial de alimentos, gosto e gastronomia. O artigo se encerra com um rápido balanço crítico da historiografia brasileira sobre o tema

Scaffold Matcher: A CMA-ES based algorithm for identifying hotspot aligned peptidomimetic scaffolds (datasets)

Datafiles used to reproduce the results in the "Scaffold Matcher: A CMA-ES based algorithm for identifying hotspot aligned peptidomimetic scaffolds" publication. Contains input files as well as files generated by the algorithm. Details can be found in the manuscript. SARSCoV19_mProFiles.zip : PDB formatted inputs and top model for SARS-CoV2 mPro. ScaffoldMatcherBenchmarkFiles_20230410.zip : PDB formatted benchmark inputs and top models

The structure of calpain and calpastatin.

<p>(A)The calpain-1 DI-DVI (green) with calpain-4 DVI (cyan) with a calpastatin subdomains A,B, and C (magenta). Dashed lines are where there was no density in the crystal structure for calpastatin. (B) Enlarged view of the interaction between subdomain C of calpastatin and DVI of calpain-4 indicated in A by black square.</p

The structures of the example NCCA side chains.

<p>The structure of α-methyl-tryptophan is shown in a dipeptide context with φ = −150 and ψ = 150 (A). Plots of backbone the energy landscape of α-methyl-tryptophan and tryptophan (left) and canonical tryptophan (right) as calculated by Rosetta (B). Calculations were done in a didpeptide context where the backbone φ and ψ were fixed, the side chain was repacked and minimized for each φ and ψ bin in 5 degree intervals. Colors represent energy of the didpeptide in kcals/mol with red being the lowest energy and most preferred backbone conformation. The structure of homoserine in a didpeptide context with φ = −150 and ψ = 150 (C). The structure of 2-indynal-glycine is shown in a dipeptide context with φ = −150 and ψ = 150 (D). The different pucker state of the five member ring of 2-indynal glycine are modeled as separate amino acid type by Rosetta because of the difficulty in using rotamer libraries to capture coordinated movements that involved simultaneous rotation about multiple dihedral angles. There is a 1.45 kcal/mol energy difference between the “exo” conformer (left) and the “endo” conformer (right) with the “endo” conformer lower in energy.</p

Summary of the Rosetta energy predictions for the redesign of the calpain/calpastatin interface and experimentally determined disassociation constants.

<p>Summary of the Rosetta energy predictions for the redesign of the calpain/calpastatin interface and experimentally determined disassociation constants.</p