Arthur Olson - Academia.edu (original) (raw)

Papers by Arthur Olson

Nature Methods, Dec 1, 2014

cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10 −7... more cellPACK assembles computational models of the biological mesoscale, an intermediate scale (10 −7-10 −8 m) between molecular and cellular biology. cellPACK's modular architecture unites existing and novel packing algorithms to generate, visualize and analyze comprehensive 3D models of complex biological environments that integrate data from multiple experimental systems biology and structural biology sources. cellPACK is currently available as open source code, with tools for validation of models and with recipes and models for five biological systems: blood plasma, cytoplasm, synaptic vesicles, HIV and a mycoplasma cell. We have applied cellPACK to model distributions of HIV envelope protein to test several hypotheses for consistency with experimental observations. Biologists, educators, and outreach specialists can interact with cellPACK models, develop new recipes and perform packing experiments through scripting and graphical user interfaces at http://cellPACK.org. Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:

Frontiers in Bioinformatics, 2021

CellPAINT is an interactive digital tool that allows non-expert users to create illustrations of ... more CellPAINT is an interactive digital tool that allows non-expert users to create illustrations of the molecular structure of cells and viruses. We present a new release with several key enhancements, including the ability to generate custom ingredients from structure information in the Protein Data Bank, and interaction, grouping, and locking functions that streamline the creation of assemblies and illustration of large, complex scenes. An example of CellPAINT as a tool for hypothesis generation in the interpretation of cryoelectron tomograms is presented. CellPAINT is freely available at http://ccsb.scripps.edu/cellpaint.

36th Annual Hawaii International Conference on System Sciences, 2003. Proceedings of the, 2003

Protein Science, 2020

The AutoDock suite provides a comprehensive toolset for computational ligand docking and drug des... more The AutoDock suite provides a comprehensive toolset for computational ligand docking and drug design and development. The suite builds on 30 years of methods development, including empirical free energy force fields, docking engines, methods for site prediction, and interactive tools for visualization and analysis. Specialized tools are available for challenging systems, including covalent inhibitors, peptides, compounds with macrocycles, systems where ordered hydration plays a key role, and systems with substantial receptor flexibility. All methods in the AutoDock suite are freely available for use and reuse, which has engendered the continued growth of a diverse community of primary users and third‐party developers.

IEEE Transactions on Visualization and Computer Graphics, 2019

Fig. 1: Multi-scale and multi-instance labeling of an HIV dataset that has thousands of copies (i... more Fig. 1: Multi-scale and multi-instance labeling of an HIV dataset that has thousands of copies (instances) of approximately 60 unique geometries: the foreground objects are automatically selected representative instances annotated with protein types, while the background objects are labeled with names of whole compartments, representing higher levels of the hierarchy.

IEEE Transactions on Visualization and Computer Graphics, 2017

We present the first approach to integrative structural modeling of the biological mesoscale with... more We present the first approach to integrative structural modeling of the biological mesoscale within an interactive visual environment. These complex models can comprise up to millions of molecules with defined atomic structures, locations, and interactions. Their construction has previously been attempted only within a non-visual and non-interactive environment. Our solution unites the modeling and visualization aspect, enabling interactive construction of atomic resolution mesoscale models of large portions of a cell. We present a novel set of GPU algorithms that build the basis for the rapid construction of complex biological structures. These structures consist of multiple membrane-enclosed compartments including both soluble molecules and fibrous structures. The compartments are defined using volume voxelization of triangulated meshes. For membranes, we present an extension of the Wang Tile concept that populates the bilayer with individual lipids. Soluble molecules are populated within compartments using the Halton sequence for their distribution. Fibrous structures, such as RNA or actin filaments, are created by self-avoiding random walks. Resulting overlaps of molecules are resolved by a forced-based system. Our approach opens new possibilities to the world of interactive construction of cellular compartments. We demonstrate its effectiveness by showcasing scenes of different scale and complexity that comprise blood plasma, mycoplasma, and HIV.

Nature protocols, 2016

Computational docking can be used to predict bound conformations and free energies of binding for... more Computational docking can be used to predict bound conformations and free energies of binding for small-molecule ligands to macromolecular targets. Docking is widely used for the study of biomolecular interactions and mechanisms, and it is applied to structure-based drug design. The methods are fast enough to allow virtual screening of ligand libraries containing tens of thousands of compounds. This protocol covers the docking and virtual screening methods provided by the AutoDock suite of programs, including a basic docking of a drug molecule with an anticancer target, a virtual screen of this target with a small ligand library, docking with selective receptor flexibility, active site prediction and docking with explicit hydration. The entire protocol will require ∼5 h.

Journal of Biocommunication, 2016

Physical models have a long and important role in exploring and communicating scientific and medi... more Physical models have a long and important role in exploring and communicating scientific and medical concepts and structures. One of the earliest physical scientific visualizations was the orrery, a mechanical model of the solar system, which first appeared in Greece around 150 BC. Early anatomical models, such as those made from Papier-Mache were developed in the early 19th Century. The earliest molecular models were those produced in the mid 19th century by chemists (such as Hoffman and Kekule) to visualize the nature of chemical composition. These models brought abstract or unseen structures into the context of human experience.

PLOS Computational Biology, 2015

Automated docking of drug-like molecules into receptors is an essential tool in structurebased dr... more Automated docking of drug-like molecules into receptors is an essential tool in structurebased drug design. While modeling receptor flexibility is important for correctly predicting ligand binding, it still remains challenging. This work focuses on an approach in which receptor flexibility is modeled by explicitly specifying a set of receptor side-chains a-priori. The challenges of this approach include the: 1) exponential growth of the search space, demanding more efficient search methods; and 2) increased number of false positives, calling for scoring functions tailored for flexible receptor docking. We present AutoDockFR-AutoDock for Flexible Receptors (ADFR), a new docking engine based on the AutoDock4 scoring function, which addresses the aforementioned challenges with a new Genetic Algorithm (GA) and customized scoring function. We validate ADFR using the Astex Diverse Set, demonstrating an increase in efficiency and reliability of its GA over the one implemented in AutoDock4. We demonstrate greatly increased success rates when cross-docking ligands into apo receptors that require side-chain conformational changes for ligand binding. These cross-docking experiments are based on two datasets: 1) SEQ17-a receptor diversity set containing 17 pairs of apo-holo structures; and 2) CDK2-a ligand diversity set composed of one CDK2 apo structure and 52 known bound inhibitors. We show that, when cross-docking ligands into the apo conformation of the receptors with up to 14 flexible side-chains, ADFR reports more correctly cross-docked ligands than AutoDock Vina on both datasets with solutions found for 70.6% vs. 35.3% systems on SEQ17, and 76.9% vs. 61.5% on CDK2. ADFR also outperforms AutoDock Vina in number of top ranking solutions on both datasets. Furthermore, we show that correctly docked CDK2 complexes recreate on average 79.8% of all pairwise atomic interactions between the ligand and moving receptor atoms in the holo complexes. Finally, we show that down-weighting the receptor internal energy improves the ranking of correctly docked poses and that runtime for AutoDockFR scales linearly when side-chain flexibility is added.

Expert Opinion on Drug Discovery, 2010

Importance to the field-Virtual screening is a computer-based technique for identifying promising... more Importance to the field-Virtual screening is a computer-based technique for identifying promising compounds to bind to a target molecule of known structure. Given the rapidly increasing number of protein and nucleic acid structures, virtual screening continues to grow as an effective method for the discovery of new inhibitors and drug molecules. Areas covered in this review-We describe virtual screening methods that are available in the AutoDock suite of programs, and several of our successes in using AutoDock virtual screening in pharmaceutical lead discovery. What the reader will gain-A general overview of the challenges of virtual screening is presented, along with the tools available in the AutoDock suite of programs for addressing these challenges. Take home message-Virtual screening is an effective tool for the discovery of compounds for use as leads in drug discovery, and the free, open source program AutoDock is an effective tool for virtual screening.

11th Symposium on Haptic Interfaces for Virtual Environment and Teleoperator Systems, 2003. HAPTICS 2003. Proceedings.

Physical models such as ball-and-stick have long been used in teaching basic chemistry and struct... more Physical models such as ball-and-stick have long been used in teaching basic chemistry and structural molecular biology. As the size and complexity of known molecular structures increases, it is difficult if not impossible to show all of their features in a physical model alone. Recent advances in automated model fabrication technology now afford physical models of more complex molecular structures. In this multi-institutional collaborative project we are creating multi-modality enhancements of such tangible models by superimposing graphical (augmented reality) information on top of the fabricated physical models, by incorporating support for voice commands, and by providing haptic feedback. The user of such an interface can request a variety of overlay representations and can interact with these virtual enhancements haptically while manipulating the physical model. This multi-modality interface appears to be quite intuitive for observing complex molecular structure. We are currently evaluating its usefulness in teaching molecular biology to high school students.

ACM SIGGRAPH 2004 Sketches on - SIGGRAPH '04, 2004

Structure, 2011

Increasingly complex research has made it more difficult to prepare data for publication, educati... more Increasingly complex research has made it more difficult to prepare data for publication, education, and outreach. Many scientists must also wade through black-box code to interface computational algorithms from diverse sources to supplement their bench work. To reduce these barriers we have developed an opensource plug-in, embedded Python Molecular Viewer (ePMV), that runs molecular modeling software directly inside of professional 3D animation applications (hosts) to provide simultaneous access to the capabilities of these newly connected systems. Uniting host and scientific algorithms into a single interface allows users from varied backgrounds to assemble professional quality visuals and to perform computational experiments with relative ease. By enabling easy exchange of algorithms, ePMV can facilitate interdisciplinary research, smooth communication between broadly diverse specialties, and provide a common platform to frame and visualize the increasingly detailed intersection(s) of cellular and molecular biology.

Structure, 2005

perceptual cues to our ability to understand 3D forms, and to perform physical manipulations, but... more perceptual cues to our ability to understand 3D forms, and to perform physical manipulations, but are curand Arthur Olson 1, * rently underutilized in most computational activities, The Scripps Research Institute including structural molecular biology. Recently, the La Jolla, California 92037 concept has arisen that the "sixth sense" of body awareness may play a critical role in our fundamental understanding of physical laws (Smetacek and Mechs-Summary ner, 2004). Thus, physical models may provide an enhanced perceptual experience in our comprehension of The evolving technology of computer autofabrication molecular structure and interaction. Early structure remakes it possible to produce physical models for search relied heavily on physical models: Pauling used complex biological molecules and assemblies. Aughis newly-invented space-filling models to depict the mented reality has recently developed as a computer molecular structures that he solved by crystallography interface technology that enables the mixing of realand to predict the basic folding units of protein strucworld objects and computer-generated graphics. We tures (Pauling and Corey, 1950). Watson and Crick used report an application that demonstrates the use of aubrass-wire molecular models to help them devise an tofabricated tangible models and augmented reality atomic model of the of DNA double helix (Watson and for research and communication in molecular biol-Crick, 1953), which reconciled decades of genetic data. ogy. We have extended our molecular modeling envi-These researchers "thought with their hands" by using ronment, PMV, to support the fabrication of a wide physical analogs to produce important scientific revariety of physical molecular models, and have sults. Current research in molecular biology now foadapted an augmented reality system to allow virtual cuses on larger assemblies and on more complex 3D representations to be overlaid onto the tangible interactions, for which the traditional atom-based physmolecular models. Users can easily change the overical models are inadequate. laid information, switching between different repre-The evolving technology of computer autofabrication sentations of the molecule, displays of molecular ("3D printing") now makes it possible to produce physiproperties, or dynamic information. The physical cal models for complex molecular assemblies (Olson, models provide a powerful, intuitive interface for ma-2001). Computer autofabrication technology, somenipulating the computer models, streamlining the times called "solid" or 3D printing (Burns, 1993) has interface between human intent, the physical model, evolved over the last decade from a rapid prototyping and the computational activity. tool for product design and manufacture to a class of more broadly applied output devices used in many

Proteins: Structure, Function, and Bioinformatics, 2002

The interaction of the αLβ2 integrin with its cellular ligand the intercellular adhesion molecule... more The interaction of the αLβ2 integrin with its cellular ligand the intercellular adhesion molecule‐1 (ICAM‐1) is critical for the tight binding interaction between most leukocytes and the vascular endothelium before transendothelial migration to the sites of inflammation. In this article we have modeled the αL subunit I‐domain in its active form, which was computationally docked with the D1 domain of the ICAM‐1 to probe potential protein‐protein interactions. The experimentally observed key interaction between the carboxylate of Glu 34 in the ICAM‐1 D1 domain and the metal ion‐dependent adhesion site (MIDAS) in the open αL I‐domain was consistently reproduced by our calculations. The calculations reveal the nature of the αLβ2/ICAM‐1 interaction and suggest an explanation for the increased ligand‐binding affinity in the “open” versus the “closed” conformation of the αL I‐domain. A mechanism for substrate selectivity among αL, αM, and α2 I‐domains is suggested whereby the orientation o...

Proteins: Structure, Function, and Genetics, 2002

Drug-resistant strains are rapidly selected during AIDS therapy because of the high rate of mutat... more Drug-resistant strains are rapidly selected during AIDS therapy because of the high rate of mutation in HIV. In this report, we present an evolutionary simulation method for analysis of viral mutation and its use for optimization of HIV-1 protease drugs to improve their robustness in the face of resistance mutation. We first present an analysis of the range of resistant mutants that produce viable viruses by using a volume-based viral fitness model. Then, we analyze how this range of mutant proteases allows development of resistance to an optimal inhibitor previously designed by computational coevolution techniques. Finally, we evaluate the resistance patterns of commercially available drugs, and we discuss how resistance might be overcome by optimizing the size of specific sidechains of these inhibitors. Proteins 2002;48:63-74.

Nature Methods, 2010

Structural biology is rapidly accumulating a wealth of detailed information about protein functio... more Structural biology is rapidly accumulating a wealth of detailed information about protein function, binding sites, RNA, large assemblies and molecular motions. These data are increasingly of interest to a broader community of life scientists, not just structural experts. Visualization is a primary means for accessing and using these data, yet visualization is also a stumbling block that prevents many life scientists from benefiting from three-dimensional structural data. In this review, we focus on key biological questions where visualizing three-dimensional structures can provide insight and describe available methods and tools. nature methods supplement | vol.7 No.3s | march 2010 | S43 review structure and so on). It is beyond the scope of this review to comprehensively compare all of these tools; instead, we focus on key biological questions for which visualizing structures can provide insight, and we highlight practical methods and tools with outstanding features that are particularly suited to addressing these questions. protein structures Finding three-dimensional structures. For a biochemist looking to use three-dimensional structures to gain insight into the functions of a particular protein, the typical first step is a search for relevant structures. This task is considerably simplified by the remarkable degree to which all experimentally determined table 1 | Selected resources for finding and visualizing macromolecules name Cost os description url stand-alone Amira $ Win, Mac, Linux Combines many different methods and scripting (EDM, MRI, optical) http://www.amiravis.com/ Cn3D 17