Side-chain Packing Using SE(3)-Transformer.

Predicting protein side-chains is important for both protein structure prediction and protein design. Modeling approaches to predict side-chains such as SCWRL4 have become one of the most widely used tools of its type due to fast and highly accurate predictions. Motivated by the recent success of AlphaFold2 in CASP14, our group adapted a 3D equivariant neural network architecture to predict protein side-chain conformations, specifically within a protein-protein interface, a problem that has not been fully addressed by AlphaFold2.

Development of a dynamic water budget model for Abu Dhabi Emirate, UAE.

In this study, a dynamic water budget model is developed for the Emirate of Abu Dhabi (EAD) in the United Arab Emirates (UAE). The model, called Abu Dhabi Water Budget Model (ADWBM), accounts for a number of drivers such as population growth, economic growth, consumption pattern and climatic factors. Model formulation, calibration, validation as well as simulation results for two future situations are presented in this paper. The two water simulations discuss demand-side options in response to different future water conditions until 2050. The first simulation, namely, baseline (BL) simulation examined water balance in the emirate assuming no change in both water production and consumption. BL simulation results highlight the expected shortages in water resources assuming no modification in the supply side. The second simulation, a more conservative and practical simulation considering water conservation options and sustainable improvements to the supply side was developed to achieve a balanced water budget by reducing the baseline consumption rates. The results show that a significant demand reduction is needed in all demand sectors, reaching 60% in the potable sectors and above 70% in non-potable sectors. Overall, results show that the ADWBM can be used as a numerical tool to produce accurate figures of water supply and demand for the sake of planning and decision making in the water sector of the EAD until 2050.

Greywater reuse through a bioretention system prototype in the arid region.

The concept of a greywater-fed bioretention system in arid regions was investigated in this study. Bioretention systems are conventionally used as a source control mechanism for urban runoff. Nevertheless, in arid regions, where rain and urban runoff are not an abundant water resource, their application is limited. Greywater (residential wastewater without toilet and kitchen sources) is comparatively less polluted and has the potential for reuse in irrigation and non-potable water uses. However, selection of an appropriate treatment is a challenge. A prototype bioretention system was made and its ability to improve greywater quality was monitored for more than 10 consecutive days. A vegetative and non-vegetative system were monitored separately. After 24 hours of retention in both systems, greywater quality was improved significantly. Both systems performed almost equally well; however, the vegetative system (with canary reed grass, Phalaris arundinacea) was found to be more effective in reducing the sodium and chemical oxygen demand contents. The study revealed that the concept of the greywater-fed bioretention system has the potential to add multi-functional benefits (greywater treatment, water conservation, landscape aesthetic and biodiversity) to the arid regions' urban environment.

Statistical downscaling of CMIP5 outputs for projecting future changes in rainfall in the Onkaparinga catchment.

A generalized linear model was fitted to stochastically downscaled multi-site daily rainfall projections from CMIP5 General Circulation Models (GCMs) for the Onkaparinga catchment in South Australia to assess future changes to hydrologically relevant metrics. For this purpose three GCMs, two multi-model ensembles (one by averaging the predictors of GCMs and the other by regressing the predictors of GCMs against reanalysis datasets) and two scenarios (RCP4.5 and RCP8.5) were considered. The downscaling model was able to reasonably reproduce the observed historical rainfall statistics when the model was driven by NCEP reanalysis datasets. Significant bias was observed in the rainfall when downscaled from historical outputs of GCMs. Bias was corrected using the Frequency Adapted Quantile Mapping technique. Future changes in rainfall were computed from the bias corrected downscaled rainfall forced by GCM outputs for the period 2041-2060 and these were then compared to the base period 1961-2000. The results show that annual and seasonal rainfalls are likely to significantly decrease for all models and scenarios in the future. The number of dry days and maximum consecutive dry days will increase whereas the number of wet days and maximum consecutive wet days will decrease. Future changes of daily rainfall occurrence sequences combined with a reduction in rainfall amounts will lead to a drier catchment, thereby reducing the runoff potential. Because this is a catchment that is a significant source of Adelaide's water supply, irrigation water and water for maintaining environmental flows, an effective climate change adaptation strategy is needed in order to face future potential water shortages.

Accelerated Molecular Mechanical and Solvation Energetics on Multicore CPUs and Manycore GPUs.

MOTIVATION: Despite several reported acceleration successes of programmable GPUs (Graphics Processing Units) for molecular modeling and simulation tools, the general focus has been on fast computation with small molecules. This was primarily due to the limited memory size on the GPU. Moreover simultaneous use of CPU and GPU cores for a single kernel execution - a necessity for achieving high parallelism - has also not been fully considered. RESULTS: We present fast computation methods for molecular mechanical (Lennard-Jones and Coulombic) and generalized Born solvation energetics which run on commodity multicore CPUs and manycore GPUs. The key idea is to trade off accuracy of pairwise, long-range atomistic energetics for higher speed of execution. A simple yet efficient CUDA kernel for GPU acceleration is presented which ensures high arithmetic intensity and memory efficiency. Our CUDA kernel uses a cache-friendly, recursive and linear-space octree data structure to handle very large molecular structures with up to several million atoms. Based on this CUDA kernel, we present a hybrid method which simultaneously exploits both CPU and GPU cores to provide the best performance based on selected parameters of the approximation scheme. Our CUDA kernels achieve more than two orders of magnitude speedup over serial computation for many of the molecular energetics terms. The hybrid method is shown to be able to achieve the best performance for all values of the approximation parameter. AVAILABILITY: The source code and binaries are freely available as PMEOPA (Parallel Molecular Energetic using Octree Pairwise Approximation) and downloadable from http://cvcweb.ices.utexas.edu/software.

Efficient Maintenance and Update of Nonbonded Lists in Macromolecular Simulations.

Molecular mechanics and dynamics simulations use distance based cutoff approximations for faster computation of pairwise van der Waals and electrostatic energy terms. These approximations traditionally use a precalculated and periodically updated list of interacting atom pairs, known as the "nonbonded neighborhood lists" or nblists, in order to reduce the overhead of finding atom pairs that are within distance cutoff. The size of nblists grows linearly with the number of atoms in the system and superlinearly with the distance cutoff, and as a result, they require significant amount of memory for large molecular systems. The high space usage leads to poor cache performance, which slows computation for large distance cutoffs. Also, the high cost of updates means that one cannot afford to keep the data structure always synchronized with the configuration of the molecules when efficiency is at stake. We propose a dynamic octree data structure for implicit maintenance of nblists using space linear in the number of atoms but independent of the distance cutoff. The list can be updated very efficiently as the coordinates of atoms change during the simulation. Unlike explicit nblists, a single octree works for all distance cutoffs. In addition, octree is a cache-friendly data structure, and hence, it is less prone to cache miss slowdowns on modern memory hierarchies than nblists. Octrees use almost 2 orders of magnitude less memory, which is crucial for simulation of large systems, and while they are comparable in performance to nblists when the distance cutoff is small, they outperform nblists for larger systems and large cutoffs. Our tests show that octree implementation is approximately 1.5 times faster in practical use case scenarios as compared to nblists.

Protein-protein docking with F(2)Dock 2.0 and GB-rerank.

MOTIVATION: Computational simulation of protein-protein docking can expedite the process of molecular modeling and drug discovery. This paper reports on our new F(2) Dock protocol which improves the state of the art in initial stage rigid body exhaustive docking search, scoring and ranking by introducing improvements in the shape-complementarity and electrostatics affinity functions, a new knowledge-based interface propensity term with FFT formulation, a set of novel knowledge-based filters and finally a solvation energy (GBSA) based reranking technique. Our algorithms are based on highly efficient data structures including the dynamic packing grids and octrees which significantly speed up the computations and also provide guaranteed bounds on approximation error. RESULTS: The improved affinity functions show superior performance compared to their traditional counterparts in finding correct docking poses at higher ranks. We found that the new filters and the GBSA based reranking individually and in combination significantly improve the accuracy of docking predictions with only minor increase in computation time. We compared F(2) Dock 2.0 with ZDock 3.0.2 and found improvements over it, specifically among 176 complexes in ZLab Benchmark 4.0, F(2) Dock 2.0 finds a near-native solution as the top prediction for 22 complexes; where ZDock 3.0.2 does so for 13 complexes. F(2) Dock 2.0 finds a near-native solution within the top 1000 predictions for 106 complexes as opposed to 104 complexes for ZDock 3.0.2. However, there are 17 and 15 complexes where F(2) Dock 2.0 finds a solution but ZDock 3.0.2 does not and vice versa; which indicates that the two docking protocols can also complement each other. AVAILABILITY: The docking protocol has been implemented as a server with a graphical client (TexMol) which allows the user to manage multiple docking jobs, and visualize the docked poses and interfaces. Both the server and client are available for download. Server: http://www.cs.utexas.edu/~bajaj/cvc/software/f2dock.shtml. Client: http://www.cs.utexas.edu/~bajaj/cvc/software/f2dockclient.shtml.

F2Dock: fast Fourier protein-protein docking.

The functions of proteins are often realized through their mutual interactions. Determining a relative transformation for a pair of proteins and their conformations which form a stable complex, reproducible in nature, is known as docking. It is an important step in drug design, structure determination, and understanding function and structure relationships. In this paper, we extend our nonuniform fast Fourier transform-based docking algorithm to include an adaptive search phase (both translational and rotational) and thereby speed up its execution. We have also implemented a multithreaded version of the adaptive docking algorithm for even faster execution on multicore machines. We call this protein-protein docking code F2Dock (F2 = Fast Fourier). We have calibrated F2Dock based on an extensive experimental study on a list of benchmark complexes and conclude that F2Dock works very well in practice. Though all docking results reported in this paper use shape complementarity and Coulombic-potential-based scores only, F2Dock is structured to incorporate Lennard-Jones potential and reranking docking solutions based on desolvation energy .

A dynamic data structure for flexible molecular maintenance and informatics.

MOTIVATION: We present the 'Dynamic Packing Grid' (DPG), a neighborhood data structure for maintaining and manipulating flexible molecules and assemblies, for efficient computation of binding affinities in drug design or in molecular dynamics calculations. RESULTS: DPG can efficiently maintain the molecular surface using only linear space and supports quasi-constant time insertion, deletion and movement (i.e. updates) of atoms or groups of atoms. DPG also supports constant time neighborhood queries from arbitrary points. Our results for maintenance of molecular surface and polarization energy computations using DPG exhibit marked improvement in time and space requirements. AVAILABILITY: http://www.cs.utexas.edu/~bajaj/cvc/software/DPG.shtml.

Cache-oblivious dynamic programming for bioinformatics.

We present efficient cache-oblivious algorithms for some well-studied string problems in bioinformatics including the longest common subsequence, global pairwise sequence alignment and three-way sequence alignment (or median), both with affine gap costs, and RNA secondary structure prediction with simple pseudoknots. For each of these problems, we present cache-oblivious algorithms that match the best-known time complexity, match or improve the best-known space complexity, and improve significantly over the cache-efficiency of earlier algorithms. We present experimental results which show that our cache-oblivious algorithms run faster than software and implementations based on previous best algorithms for these problems.