Atomic detail visualization of photosynthetic membranes with GPU-accelerated ray tracing

The cellular process responsible for providing energy for most life on Earth, namely, photosynthetic light-harvesting, requires the cooperation of hundreds of proteins across an organelle, involving length and time scales spanning several orders of magnitude over quantum and classical regimes. Simulation and visualization of this fundamental energy conversion process pose many unique methodological and computational challenges. We present, in two accompanying movies, light-harvesting in the photosynthetic apparatus found in purple bacteria, the so-called chromatophore. The movies are the culmination of three decades of modeling efforts, featuring the collaboration of theoretical, experimental, and computational scientists. We describe the techniques that were used to build, simulate, analyze, and visualize the structures shown in the movies, and we highlight cases where scientific needs spurred the development of new parallel algorithms that efficiently harness GPU accelerators and petascale computers

Ray Tracing Gems

This book is a must-have for anyone serious about rendering in real time. With the announcement of new ray tracing APIs and hardware to support them, developers can easily create real-time applications with ray tracing as a core component. As ray tracing on the GPU becomes faster, it will play a more central role in real-time rendering. Ray Tracing Gems provides key building blocks for developers of games, architectural applications, visualizations, and more. Experts in rendering share their knowledge by explaining everything from nitty-gritty techniques that will improve any ray tracer to mastery of the new capabilities of current and future hardware. What you'll learn: The latest ray tracing techniques for developing real-time applications in multiple domains Guidance, advice, and best practices for rendering applications with Microsoft DirectX Raytracing (DXR) How to implement high-performance graphics for interactive visualizations, games, simulations, and more Who this book is for: Developers who are looking to leverage the latest APIs and GPU technology for real-time rendering and ray tracing Students looking to learn about best practices in these areas Enthusiasts who want to understand and experiment with their new GPU

Protein Structure

Since the dawn of recorded history, and probably even before, men and women have been grasping at the mechanisms by which they themselves exist. Only relatively recently, did this grasp yield anything of substance, and only within the last several decades did the proteins play a pivotal role in this existence. In this expose on the topic of protein structure some of the current issues in this scientific field are discussed. The aim is that a non-expert can gain some appreciation for the intricacies involved, and in the current state of affairs. The expert meanwhile, we hope, can gain a deeper understanding of the topic

Single-molecule techniques in biophysics : a review of the progress in methods and applications

Single-molecule biophysics has transformed our understanding of the fundamental molecular processes involved in living biological systems, but also of the fascinating physics of life. Far more exotic than a collection of exemplars of soft matter behaviour, active biological matter lives far from thermal equilibrium, and typically covers multiple length scales from the nanometre level of single molecules up several orders of magnitude to longer length scales in emergent structures of cells, tissues and organisms. Biological molecules are often characterized by an underlying instability, in that multiple metastable free energy states exist which are separated by energy levels of typically just a few multiples of the thermal energy scale of kBT, where kB is the Boltzmann constant and T the absolute temperature, implying complex, dynamic inter-conversion kinetics across this bumpy free energy landscape in the relatively hot, wet environment of real, living biological matter. The key utility of single-molecule biophysics lies in its ability to probe the underlying heterogeneity of free energy states across a population of molecules, which in general is too challenging for conventional ensemble level approaches which measure mean average properties. Parallel developments in both experimental and theoretical techniques have been key to the latest insights and are enabling the development of highly-multiplexed, correlative techniques to tackle previously intractable biological problems. Experimentally, technological developments in the sensitivity and speed of biomolecular detectors, the stability and efficiency of light sources, probes and microfluidics, have enabled and driven the study of heterogeneous behaviours both in vitro and in vivo that were previously undetectable by ensemble methods..

Molecular modeling and simulations of viruses: structure, dynamics and antibody design

Connecting dynamics to structural data from an array of diverse yet complementary experimental sources, all-atom molecular dynamics (MD) simulations permit the exploration of biological phenomena in unparalleled detail. We employed MD simulations and molecular modeling to investigate the dynamic properties of virus capsids, to determine the atomic structure of highly-flexible capsid domains, which could not be solved using a single experimental method, and to unravel the molecular mechanisms of host-pathogen interactions. Furthermore, we have recently integrated MD simulation into a de novo antibody design program to assess the binding and thermal stabilities of the designed antibodies and to identify antibodies with high binding affinity. We first investigated a retrovirus capsid in its immature, non-infectious state. For a retrovirus to be infectious, the immature retrovirus has to undergo maturation where the immature capsid proteins, also known as Gag, are cleaved proteolytically and then rearranged to form a mature capsid. Obtaining an atomic structure of the immature capsid has been elusive for many years. Recent advances in cryo-electron microscopy have yielded high resolution density maps and therefore enabled accurate computational modelings and simulations. We report the first atomic model of an immature Gag lattice, using Rous sarcoma virus (RSV) as the model system. The model includes an atomic model of a flexible domain called spacer peptide. The immature Gag lattice model was obtained using homology modeling and microsecond-long MD simulations and was tested via mutagenesis experiments in vitro. Upon obtaining the atomic structure of immature RSV lattice, we characterized the roles of key charged residues of RSV by simulating the wild type and mutant structures. We discovered a novel allosteric pathway that could explain how a mutation could suppress the detrimental effect of another mutation despite being 20 Angstrom apart. The human body has two types of immune systems to prevent and combat viral infection: innate and adaptive immune systems. Lung surfactant proteins are part of the innate immune system, and they act at the front-end of the host defense. Surfactant proteins A (SP-A) and D (SP-D) protect humans from bacterial infection and influenza A virus, respectively. Using structural information from X-ray crystallography, we probe the interactions between SP-D and influenza A virus at the atomic level. Our simulation results show that a double mutant of SP-D binds stronger to influenza A virus using a different binding loop than the wild type SP-D. Additionally, the lipid binding properties of SP-A were probed using MD simulations and mutational studies. We found a non-canonical lipid binding site with several critical binding features that involve cation-π interactions. Steered MD simulations also revealed that SP-A binds to bacterial lipid more tightly than lung surfactant. These results suggest that SP-A may transfer from surfactant to bacterial membranes to initiate its host defense functions. Antibodies are secreted by a type of white blood cell called B lymphocytes, which is an important component of the adaptive immune system. Antibodies identify and neutralize pathogens such as bacteria and viruses. Developing antibodies using solely experimental methods is a time-consuming process. Therefore, computational methods have been developed to design antibodies. However, most of these computational methods lack dynamic information during the design process as only static structures are considered. To generate antibodies with high binding affinity, we incorporated MD simulation into the antibody design workflow to account for the dynamic nature of the antigen-antibody interaction. The antibody design program with the improved workflow has successfully designed high-affinity antibodies to target a small, 12-residue-long peptide antigen, and the program is currently being used to design antibodies targeting a larger antigen, namely the Ebola glycoprotein

Microscopy Conference 2017 (MC 2017) - Proceedings

Das Dokument enthält die Kurzfassungen der Beiträge aller Teilnehmer an der Mikroskopiekonferenz "MC 2017", die vom 21. bis 25.08.2017, in Lausanne stattfand