Best practices for constructing, preparing, and evaluating protein-ligand binding affinity benchmarks

Free energy calculations are rapidly becoming indispensable in structure-enabled drug discovery programs. As new methods, force fields, and implementations are developed, assessing their expected accuracy on real-world systems (benchmarking) becomes critical to provide users with an assessment of the accuracy expected when these methods are applied within their domain of applicability, and developers with a way to assess the expected impact of new methodologies. These assessments require construction of a benchmark - a set of well-prepared, high quality systems with corresponding experimental measurements designed to ensure the resulting calculations provide a realistic assessment of expected performance when these methods are deployed within their domains of applicability. To date, the community has not yet adopted a common standardized benchmark, and existing benchmark reports suffer from a myriad of issues, including poor data quality, limited statistical power, and statistically deficient analyses, all of which can conspire to produce benchmarks that are poorly predictive of real-world performance. Here, we address these issues by presenting guidelines for (1) curating experimental data to develop meaningful benchmark sets, (2) preparing benchmark inputs according to best practices to facilitate widespread adoption, and (3) analysis of the resulting predictions to enable statistically meaningful comparisons among methods and force fields

Dissolution of oxygen reduction electrocatalysts in acidic environment

Platinum (Pt) alloy nanoparticles are used as catalysts in electrochemical cells to reduce oxygen to water and to oxidize hydrogen; the overall reaction converts chemical energy into electrical energy. These nanocatalysts are deposited on a carbon substrate and their catalytic function takes place in acid medium. This harsh environment causes an undesired reaction, which is the dissolution of the metal atoms into the acid medium; thus affecting the catalyst life. This dissertation aims to investigate the dissolution mechanism of fuel cell cathode catalysts at the atomic level starting from the oxygen reaction intermediates on the cathode catalyst surface and propose guidelines to improve cathode catalysts durability based on our proposed mechanism. Density functional theory is employed to study various possible scenarios with the goals of understanding the mechanism of the metal atom dissolution process and establishing some guidelines that permit a rational design of catalysts with better stability against dissolution. A thermodynamic analysis of potential metal dissolution reactions in acid medium is presented first, using density functional theory calculations to explore the relative stabilities of transition metals in relation to that of Pt. The study is performed by comparing the change in reaction Gibbs free energies for different metals in a given dissolution reaction. Then, a series of density functional theory studies, tending to investigate the adsorbed atomic oxygen absorption process from cathode catalyst surface into its subsurface, includes: 1) the oxygen adsorption on various catalyst surfaces and oxygen absorption in subsurface sites to figure out the minimum energy pathway and energy barrier of on-surface oxygen migration and absorption into subsurface; 2) the oxygen coverage, the other oxygen reduction reaction intermediates, and water effects on the oxygen absorption process according to reaction pathways, energy barriers, and thermodynamic analysis; 3) the oxygen absorption process on several Pt-based alloys with various compositions and components to find out the best alloy to inhibit atomic oxygen absorption including both kinetic and thermodynamic analyses, and the effects of such alloyed species on the inhibition process

Precision Study of Positronium: Testing Bound State QED Theory

As an unstable light pure leptonic system, positronium is a very specific probe atom to test bound state QED. In contrast to ordinary QED for free leptons, the bound state QED theory is not so well understood and bound state approaches deserve highly accurate tests. We present a brief overview of precision studies of positronium paying special attention to uncertainties of theory as well as comparison of theory and experiment. We also consider in detail advantages and disadvantages of positronium tests compared to other QED experiments.Comment: A talk presented at Workshop on Positronium Physics (ETH Zurich, May 30-31, 2003

Carbon Free Boston: Waste Technical Report

Part of a series of reports that includes: Carbon Free Boston: Summary Report; Carbon Free Boston: Social Equity Report; Carbon Free Boston: Technical Summary; Carbon Free Boston: Buildings Technical Report; Carbon Free Boston: Transportation Technical Report; Carbon Free Boston: Energy Technical Report; Carbon Free Boston: Offsets Technical Report; Available at http://sites.bu.edu/cfb/OVERVIEW: For many people, their most perceptible interaction with their environmental footprint is through the waste that they generate. On a daily basis people have numerous opportunities to decide whether to recycle, compost or throwaway. In many cases, such options may not be present or apparent. Even when such options are available, many lack the knowledge of how to correctly dispose of their waste, leading to contamination of valuable recycling or compost streams. Once collected, people give little thought to how their waste is treated. For Boston’s waste, plastic in the disposal stream acts becomes a fossil fuel used to generate electricity. Organics in the waste stream have the potential to be used to generate valuable renewable energy, while metals and electronics can be recycled to offset virgin materials. However, challenges in global recycling markets are burdening municipalities, which are experiencing higher costs to maintain their recycling. The disposal of solid waste and wastewater both account for a large and visible anthropogenic impact on human health and the environment. In terms of climate change, landfilling of solid waste and wastewater treatment generated emissions of 131.5 Mt CO2e in 2016 or about two percent of total United States GHG emissions that year. The combustion of solid waste contributed an additional 11.0 Mt CO2e, over half of which (5.9 Mt CO2e) is attributable to the combustion of plastic [1]. In Massachusetts, the GHG emissions from landfills (0.4 Mt CO2e), waste combustion (1.2 Mt CO2e), and wastewater (0.5 Mt CO2e) accounted for about 2.7 percent of the state’s gross GHG emissions in 2014 [2]. The City of Boston has begun exploring pathways to Zero Waste, a goal that seeks to systematically redesign our waste management system that can simultaneously lead to a drastic reduction in emissions from waste. The easiest way to achieve zero waste is to not generate it in the first place. This can start at the source with the decision whether or not to consume a product. This is the intent behind banning disposable items such as plastic bags that have more sustainable substitutes. When consumption occurs, products must be designed in such a way that their lifecycle impacts and waste footprint are considered. This includes making durable products, limiting the use of packaging or using organic packaging materials, taking back goods at the end of their life, and designing products to ensure compatibility with recycling systems. When reducing waste is unavoidable, efforts to increase recycling and organics diversion becomes essential for achieving zero waste. [TRUNCATED]Published versio

Efficient methods and practical guidelines for simulating isotope effects

The shift in chemical equilibria due to isotope substitution is often exploited to gain insight into a wide variety of chemical and physical processes. It is a purely quantum mechanical effect, which can be computed exactly using simulations based on the path integral formalism. Here we discuss how these techniques can be made dramatically more efficient, and how they ultimately outperform quasi-harmonic approximations to treat quantum liquids not only in terms of accuracy, but also in terms of computational efficiency. To achieve this goal we introduce path integral quantum mechanics estimators based on free energy perturbation, which enable the evaluation of isotope effects using only a single path integral molecular dynamics trajectory of the naturally abundant isotope. We use as an example the calculation of the free energy change associated with H/D and 16O/18O substitutions in liquid water, and of the fractionation of those isotopes between the liquid and the vapor phase. In doing so, we demonstrate and discuss quantitatively the relative benefits of each approach, thereby providing a set of guidelines that should facilitate the choice of the most appropriate method in different, commonly encountered scenarios. The efficiency of the estimators we introduce and the analysis that we perform should in particular facilitate accurate ab initio calculation of isotope effects in condensed phase systems

Carbon Free Boston: Buildings Technical Report

Part of a series of reports that includes: Carbon Free Boston: Summary Report; Carbon Free Boston: Social Equity Report; Carbon Free Boston: Technical Summary; Carbon Free Boston: Transportation Technical Report; Carbon Free Boston: Waste Technical Report; Carbon Free Boston: Energy Technical Report; Carbon Free Boston: Offsets Technical Report; Available at http://sites.bu.edu/cfb/OVERVIEW: Boston is known for its historic iconic buildings, from the Paul Revere House in the North End, to City Hall in Government Center, to the Old South Meeting House in Downtown Crossing, to the African Meeting House on Beacon Hill, to 200 Clarendon (the Hancock Tower) in Back Bay, to Abbotsford in Roxbury. In total, there are over 86,000 buildings that comprise more than 647 million square feet of area. Most of these buildings will still be in use in 2050. Floorspace (square footage) is almost evenly split between residential and non-residential uses, but residential buildings account for nearly 80,000 (93 percent) of the 86,000 buildings. Boston’s buildings are used for a diverse range of activities that include homes, offices, hospitals, factories, laboratories, schools, public service, retail, hotels, restaurants, and convention space. Building type strongly influences energy use; for example, restaurants, hospitals, and laboratories have high energy demands compared to other commercial uses. Boston’s building stock is characterized by thousands of turn-of-the-20th century homes and a postWorld War II building boom that expanded both residential buildings and commercial space. Boston is in the midst of another boom in building construction that is transforming neighborhoods across the city. [TRUNCATED]Published versio

Optimizing Radiant Systems for Energy Efficiency and Comfort

Radiant cooling and heating systems provide an opportunity to achieve significant energy savings, peak demand reduction, load shifting, and thermal comfort improvements compared to conventional all-air systems. As a result, application of these systems has increased in recent years, particularly in zero-net-energy (ZNE) and other advanced low-energy buildings. Despite this growth, completed installations to date have demonstrated that controls and operation of radiant systems can be challenging due to a lack of familiarity within the heating, ventilation, and air-conditioning (HVAC) design and operations professions, often involving new concepts (particularly related to the slow response in high thermal mass radiant systems). To achieve the significant reductions in building energy use proposed by California Public Utilities Commission’s (CPUC’s) Energy Efficiency Strategic Plan that all new non-residential buildings be ZNE by 2030, it is critical that new technologies that will play a major role in reaching this goal be applied in an effective manner. This final report describes the results of a comprehensive multi-faceted research project that was undertaken to address these needed enhancements to radiant technology by developing the following: (1) sizing and operation tools (currently unavailable on the market) to provide reliable methods to take full advantage of the radiant systems to provide improved energy performance while maintaining comfortable conditions, (2) energy, cost, and occupant comfort data to provide real world examples of energy efficient, affordable, and comfortable buildings using radiant systems, and (3) Title-24 and ASHRAE Standards advancements to enhance the building industry’s ability to achieve significant energy efficiency goals in California with radiant systems. The research team used a combination of full-scale fundamental laboratory experiments, whole-building energy simulations and simplified tool development, and detailed field studies and control demonstrations to assemble the new information, guidance and tools necessary to help the building industry achieve significant energy efficiency goals for radiant systems in California

[Report of] Specialist Committee V.4: ocean, wind and wave energy utilization

The committee's mandate was :Concern for structural design of ocean energy utilization devices, such as offshore wind turbines, support structures and fixed or floating wave and tidal energy converters. Attention shall be given to the interaction between the load and the structural response and shall include due consideration of the stochastic nature of the waves, current and wind

Variation in carbon footprint of milk due to management differences between Swedish dairy farms

To identify mitigation options to reduce greenhouse gas (GHG) emissions from milk production (i.e. the carbon footprint (CF) of milk), this study examined the variation in GHG emissions among dairy farms using data from previous CF studies on Swedish milk. Variation between farms in these production data, which were found to have a strong influence on milk CF were obtained from existing databases of e.g. 1051 dairy farms in Sweden in 2005. Monte Carlo analysis was used to analyse the impact of variations in seven important parameters on milk CF concerning milk yield (energy corrected milk (ECM) produced and delivered), feed dry matter intake (DMI), enteric methane emissions, N content in feed DMI, N-fertiliser rate and diesel used on farm. The largest between farm variation among the analysed production data were N-fertiliser rate (kg/ha) and diesel used (l/ha) on farm (coefficient of variation (CV) 31-38%). For the parameters concerning milk yield and feed DMI the CV was approx. 11 and 8%, respectively. The smallest variation in production data was found for N content in feed DMI. According to the Monte Carlo analysis, these variations in production data led to a variation in milk CF of between 0.94 and 1.33 kg CO2 equivalents (CO2e) per kg ECM, with an average value of 1.13 kg/CO2e kg ECM. We consider that this variation of ±17% that was found based on the used farm data would be even greater if all Swedish dairy farms were included, as the sample of farms in this study was not totally unbiased. The variation identified in milk CF indicates that a potential exists to reduce GHG emissions from milk production on both national and farm level through changes in management. As milk yield and feed DMI are two of the most influential parameters for milk CF, feed conversion efficiency (i.e. units ECM produced per unit DMI) can be used as a rough key performance indicator for predicting CF reductions. However, it must be borne in mind that feeds have different CF due to where and how they are produced